bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of histone deacetylase 6 attenuates intestinal inflammation and apoptosis in a rodent model of hemorrhagic shock
Authors: Chang Panpan , Bhatti Umar F. , Williams Aaron M. , Dennahy Isabel S. , Liu Baoling , Li Yongqing , Alam Hasan B. 
Published: December 2018

BACKGROUND
Intestinal inflammation is a mediator of multiorgan failure in trauma. We have previously shown that histone deacetylase (HDAC6) inhibitors, including ACY1083, improve survival and preserve intestinal tight junction integrity in a rodent model of hemorrhagic shock (HS). However, mechanisms leading to this alleviation in intestinal injury remain poorly defined. In this study, we sought to determine whether HDAC6 inhibition by ACY1083 can attenuate intestinal inflammation and apoptosis in rats subjected to HS.

METHODS
Sprague Dawley rats were subjected to hemorrhage (40% of total blood volume) followed by intravenous injection of either ACY1083 (30 mg/kg) dissolved in cyclodextrin or cyclodextrin only (vehicle group). Three hours after hemorrhage, blood samples were collected, and small bowel was harvested. Histological effects of ACY1083 on small bowel were examined. Myeloperoxidase (MPO) levels were assessed as a marker for neutrophil infiltration. Whole cell lysates were analyzed for acetylated α-tubulin, metalloproteinase (ADAM) 17, TNF-α, IL-6, and cleaved caspase 3 using Western blot. The levels of ADAM17, TNF-α, and IL-6 in serum were also examined using enzyme-linked immunosorbent assay.

RESULTS
ACY1083 treatment significantly attenuated HS-induced intestinal injury and MPO production. Both systemic and intestinal TNF-α and IL-6 levels were attenuated following ACY1083 administration. Increased acetylation of α-tubulin was observed in rats treated with ACY1083, along with a significantly decreased expression of cleaved caspase 3 following hemorrhage.

CONCLUSION
Inhibition of HDAC6 with ACY1083 provides intestinal protection by attenuating both the inflammatory and apoptotic responses during HS.
Identifying A- and P-site locations on ribosome-protected mRNA fragments using Integer Programming
Authors: Ahmed Nabeel , Sormanni Pietro , Ciryam Prajwal , Vendruscolo Michele , Dobson Christopher M. , O’Brien Edward P. 
Published: December 2018

AbstractIdentifying the A- and P-site locations on ribosome-protected mRNA fragments from Ribo-Seq experiments is a fundamental step in the quantitative analysis of transcriptome-wide translation properties at the codon level. Many analyses of Ribo-Seq data have utilized heuristic approaches applied to a narrow range of fragment sizes to identify the A-site. In this study, we use Integer Programming to identify A-site by maximizing an objective function that reflects the fact that the ribosome’s A-site on ribosome-protected fragments must reside between the second and stop codons of an mRNA. This identifies the A-site location as a function of the fragment’s size and its 5□ end reading frame in Ribo-Seq data generated from S. cerevisiae and mouse embryonic stem cells. The correctness of the identified A-site locations is demonstrated by showing that this method, as compared to others, yields the largest ribosome density at established stalling sites. By providing greater accuracy and utilization of a wider range of fragment sizes, our approach increases the signal-to-noise ratio of underlying biological signals associated with translation elongation at the codon length scale.
Clinical implications of identifying pathogenic variants in aortic dissection patients with whole exome sequencing
Authors: Wolford Brooke N. , Hornsby Whitney E. 
Published: December 2018

ABSTRACTBackgroundThoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or their family members.MethodsWe performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity.ResultsTwenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 vs. 57 years), higher rates of root aneurysm (54% vs. 30%), less hypertension (15% vs. 57%), lower rates of smoking (19% vs. 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed significant risk factors associated with pathogenic variants are age <50 [odds ratio (OR) = 5.5; 95% CI: 1.6-19.7], no history of hypertension (OR=5.6; 95% CI: 1.4-22.3) and family history of aortic disease (mother: OR=5.7; 95% CI: 1.4-22.3, siblings: OR=5.1; 95% CI 1.1-23.9, children: OR=6.0; 95% CI: 1.4-26.7).ConclusionsClinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset of aortic dissection <50 years old, family history of aortic disease, and no history of hypertension.
Species Tree Inference on Data with Paralogs is Accurate Using Methods Intended to Deal with Incomplete Lineage Sorting
Authors: Yan Zhi , Smith Megan L. , Du Peng , Hahn Matthew W. , Nakhleh Luay 
Published: December 2018

AbstractMany recent phylogenetic methods have focused on accurately inferring species trees when there is gene tree discordance due to incomplete lineage sorting (ILS). For almost all of these methods, and for phylogenetic methods in general, the data for each locus is assumed to consist of orthologous, single-copy sequences. Loci that are present in more than a single copy in any of the studied genomes are excluded from the data. These steps greatly reduce the number of loci available for analysis. The question we seek to answer in this study is: What happens if one runs such species tree inference methods on data where paralogy is present, in addition to or without ILS being present? Through simulation studies and analyses of two large biological data sets, we show that running such methods on data with paralogs can still provide accurate results. We use multiple different methods, some of which are based directly on the multispecies coalescent (MSC) model, and some of which have been proven to be statistically consistent under it. We also treat the paralogous loci in multiple ways: from explicitly denoting them as paralogs, to randomly selecting one copy per species. In all cases the inferred species trees are as accurate as equivalent analyses using single-copy orthologs. Our results have significant implications for the use of ILS-aware phylogenomic analyses, demonstrating that they do not have to be restricted to single-copy loci. This will greatly increase the amount of data that can be used for phylogenetic inference.
Access COI barcode efficiently using high throughput Single-End 400 bp sequencing
Authors: Yang Chentao , Tan Shangjin , Meng Guangliang , Bourne David G. , O’Brien Paul A. , Xu Junqiang , Liao Sha , Chen Ao , Chen Xiaowei , Liu Shanlin 
Published: December 2018

SummaryOver the last decade, the rapid development of high-throughput sequencing platforms has accelerated species description and assisted morphological classification through DNA barcoding. However, constraints in barcoding costs led to unbalanced efforts which prevented accurate taxonomic identification for biodiversity studies.We present a high throughput sequencing approach based on the HIFI-SE pipeline which takes advantage of Single-End 400 bp (SE400) sequencing data generated by BGISEQ-500 to produce full-length Cytochrome c oxidase subunit I (COI) barcodes from pooled polymerase chain reaction amplicons. HIFI-SE was written in Python and included four function modules of filter, assign, assembly and taxonomy.We applied the HIFI-SE to a test plate which contained 96 samples (30 corals, 64 insects and 2 blank controls) and delivered a total of 86 fully assembled HIFI COI barcodes. By comparing to their corresponding Sanger sequences (72 sequences available), it showed that most of the samples (98.61%, 71/72) were correctly and accurately assembled, including 46 samples that had a similarity of 100% and 25 of ca. 99%.Our approach can produce standard full-length barcodes cost efficiently, allowing DNA barcoding for global biomes which will advance DNA-based species identification for various ecosystems and improve quarantine biosecurity efforts.
Integrative analysis of Dupuytren’s disease identifies novel risk locus and reveals a shared genetic etiology with BMI
Authors: Major Megan , Freund Malika K , Burch Kathryn S , Mancuso Nicholas , Ng Michael , Furniss Dominic , Pasaniuc Bogdan , Ophoff Roel 
Published: December 2018

AbstractDupuytren’s disease is the common inherited tissue-specific fibrotic disorder. It’s characterized by progressive and irreversible fibroblastic proliferation affecting the palmar fascia of the hand, with an onset typically in the sixth decade of life. Although genome-wide association studies (GWAS) have identified 24 genomic regions associated with Dupuytren’s risk, the biological mechanisms driving signal at these regions remain elusive. We identify potential biological mechanisms for Dupuytren’s disease by integrating the most recent, largest GWAS (ncases = 3,871, ncontrols = 4,686) with eQTLs (47 tissue panels from five consortia, total n = 3,975) to perform a transcriptome-wide association study (TWAS). We identify 43 tissue-specific gene associations with Dupuytren’s risk, one of which resides at least 0.5 Mb away from the 24 risk regions previously identified. We also estimate the genome-wide genetic correlation between Dupuytren’s disease and 45 complex traits and find significant genetic correlations between Dupuytren’s disease and body mass index (, P = 1.6 × 10−6), type II diabetes (, P = 1.7 × 10−4), triglycerides (, P = 3.5 × 10−4), and high-density lipoprotein (, P = 4.1 × 10−4), which suggests a shared genetic etiology. We further refine the genome-wide genetic correlation signal to identify 8 regions significantly negatively correlated with BMI and 3 regions significantly correlated (1 positively and 2 negatively correlated) with HDL; none of these regions contained the novel gene association identified by TWAS. Our results are consistent with previous epidemiological findings which show that lower BMI increases risk for Dupuytren’s disease. These 12 novel risk regions provide new insight into the biological mechanisms of Dupuytren’s disease and serve as a starting point for functional validation.
AAV-mediated gene transfer restores a normal muscle transcriptome in a canine model of X-linked myotubular myopathy
Authors: Dupont Jean-Baptiste , Guo Jianjun , Lawlor Michael W. , Grange Robert W. , Gray John T. , Buj-Bello Ana , Childers Martin K. , Mack David L. 
Published: December 2018

AbstractMultiple clinical trials employing recombinant adeno-associated viral (rAAV) vectors have been initiated for neuromuscular disorders, including Duchenne and limb-girdle muscular dystrophies, spinal muscular atrophy, and recently X-linked myotubular myopathy (XLMTM). Previous work from our laboratory on a canine model of XLMTM showed that a single rAAV8-cMTM1 systemic infusion corrects structural abnormalities within the muscle and restores contractile function, with affected dogs surviving more than four years post injection. This exceptional therapeutic efficacy presents a unique opportunity to identify the downstream molecular drivers of XLMTM pathology, and to what extent the whole muscle transcriptome is restored to normal after gene transfer. Herein, RNA-sequencing was used to examine the transcriptomes of the Biceps femoris and Vastus lateralis in a previously-described canine cohort showing dose-dependent clinical improvements after rAAV8-cMTM1 gene transfer. Our analysis confirmed several dysregulated genes previously observed in XLMTM mice, but also identified new transcripts linked to XLMTM pathology. We demonstrated XLMTM transcriptome remodeling and dose-dependent normalization of gene expression after gene transfer and created new metrics to pinpoint potential biomarkers of disease progression and correction.
Multiple species drive flexible lake food webs with warming
Authors: Bartley Timothy J. , Tunney Tyler D. , Lester Nigel P. , Shuter Brian J. , Hanner Robert H. , McCann Kevin S. 
Published: December 2018

AbstractClimate change is rewiring the food webs that determine the fate of diverse ecosystems. Mobile generalist consumers are responding to climate change by rapidly shifting their behaviour and foraging, driving food webs to flex. Although these responsive generalists form a key stabilizing module in food web structure, the extent to which they are present throughout whole food webs is largely unknown. Here, we show that multiple species comprising key trophic roles drive flexible lake food webs with warming. By examining lakes that span a 7°C air temperature gradient, we found significant reductions in nearshore derived carbon and nearshore habitat use with increased temperature in three of four fish species. We also found evidence that the response of lake trout to increased temperatures may reduce their biomass and cascade to release their preferred prey, the pelagic forage fish cisco. Our results suggest that climate warming will shift lake food webs toward increased reliance on offshore habitats and resources. We argue that species across trophic levels broadly couple lake macrohabitats, suggesting that potentially stabilizing responsive consumers are present throughout food webs. However, climate change appears to limit their ability to responsively forage, critically undermining a repeated stabilizing mechanism in food webs.
Discovery of Hierarchical Representations for Efficient Planning
Authors: Tomov Momchil S. , Yagati Samyukta , Kumar Agni , Yang Wanqian , Gershman Samuel J. 
Published: December 2018

SummaryWe propose that humans spontaneously organize environments into clusters of states that support hierarchical planning, enabling them to tackle challenging problems by breaking them down into sub-problems at various levels of abstraction. People constantly rely on such hierarchical presentations to accomplish tasks big and small – from planning one’s day, to organizing a wedding, to getting a PhD – often succeeding on the very first attempt. We formalize a Bayesian model of hierarchy discovery that explains how humans discover such useful abstractions. Building on principles developed in structure learning and robotics, the model predicts that hierarchy discovery should be sensitive to the topological structure, reward distribution, and distribution of tasks in the environment. In five simulations, we show that the model accounts for previously reported effects of environment structure on planning behavior, such as detection of bottleneck states and transitions. We then test the novel predictions of the model in eight behavioral experiments, demonstrating how the distribution of tasks and rewards can influence planning behavior via the discovered hierarchy, sometimes facilitating and sometimes hindering performance. We find evidence that the hierarchy discovery process unfolds incrementally across trials. We also find that people use uncertainty to guide their learning in a way that is informative for hierarchy discovery. Finally, we propose how hierarchy discovery and hierarchical planning might be implemented in the brain. Together, these findings present an important advance in our understanding of how the brain might use Bayesian inference to discover and exploit the hidden hierarchical structure of the environment.
Measuring graded changes in consciousness through multi-target filling-in
Authors: Davidson Matthew J , Graafsma Irene , Tsuchiya Naotsugu , van Boxtel Jeroen 
Published: December 2018

AbstractPerceptual filling-in (PFI) occurs when a physically-present visual target disappears from conscious perception, with its location filled in by the surrounding visual background. Compared to other visual illusions, these perceptual changes are crisp and simple, and can occur for multiple spatially-separated targets simultaneously. Contrasting neural activity during the presence or absence of PFI may complement other multistable phenomena to reveal the neural correlates of consciousness (NCC). We presented four peripheral targets over a background dynamically updating at 20 Hz. While participants reported on target disappearances/reappearances via button press/release, we tracked neural activity entrained by the background during PFI using steady-state visually evoked potentials (SSVEPs) recorded in the electroencephalogram. We found background SSVEPs closely correlated with subjective report, and increased with an increasing amount of PFI. Unexpectedly, we found that as the number of filled-in targets increased, the duration of target disappearances also increased, suggesting facilitatory interactions exist between targets in separate visual quadrants. We also found distinct spatiotemporal correlates for the background SSVEP harmonics. Prior to genuine PFI, the response at the second harmonic (40 Hz) increased before the first (20 Hz), which we tentatively link to an attentional effect. There was no difference between harmonics for physically removed stimuli. These results demonstrate that PFI can be used to study multi-object perceptual suppression when frequency-tagging the background of a visual display, and because there are distinct neural correlates for endogenously and exogenously induced changes in consciousness, that it is ideally suited to study the NCC.HighlightsPerceptual filling-in (PFI) has distinct advantages for investigating the neural correlates of consciousness.Participants can accurately report graded changes in consciousness using four simultaneous buttons.Frequency-tagging of visual background information tracks changes in visual perception.Spatiotemporal EEG responses differentiate PFI from phenomenally matched physical disappearances.
Resolving conflict in organizations – achieving results through a harmonization process
Authors: Nguyen Thuc-Doan 
Published: December 2018

PurposeConflict is inevitable in organizational life. On the one hand, it can bring creativity and enhance problem-solving. On the other, it can hinder effective problem-solving, increase defensiveness and member dissatisfaction, and create a destructive work environment. This paper aims to outline four important components of harmonization that help to enhance conflict-management capability.Design/methodology/approachBased on Nguyen and Belk’s (2013) harmonization framework, the author adds their own comments and places in the context of resolving conflict in organization.FindingsThe harmonization process synthesizes multiple goals and balances differences to achieve better solutions without discounting any of these elements. Harmonization provides better understanding of important issues and why they are critical to each party. Each party will feel better about the situation after having heard the other side’s position. There might be anger, anxiety, or frustration at the beginning. However, when people successfully go through the harmonization process, they feel happy, connected to others and proud of the results they get. These processes require communicating with others, learning others’ perspectives, understanding and empathizing with others, and being willing to adjust.Practical implicationsThe paper outlines four skills in which organizations can train their employees to improve conflict management.Originality/valueHarmonization process is applied to conflict management in organization.
When institutions matter: a gravity model for Chinese meat imports
Authors: Hasiner Eva , Yu Xiaohua 
Published: December 2018

PurposeIn international trade differences in political and legal systems confront trading partners with relatively greater information asymmetry and contract enforcement problems than in domestic trade, resulting in higher transaction costs. Nevertheless, well-functioning institutions in the exporting country could prove beneficial for the agricultural importer, as institutions generally establish food and product regulations and ensure that they are enforced and serve as a last resort for dispute resolution and contract enforcement. Given China’s increasingly stricter control of its food supply chain and its rising imports of meat products, the purpose of this paper is to analyze whether institutions in the exporting country matter for Chinese meat imports.Design/methodology/approachTo analyze the effect of the exporters’ institutions on Chinese meat imports, the authors estimate a gravity model for the 1990-2013 period. The authors apply the method suggested by Helpmanet al.(2008) to correct for sample selection and firm heterogeneity. To estimate the effect of time-invariant variables, the authors apply the Fixed Effects Vector Decomposition method proposed by Plümper and Troeger (2007).FindingsThe results show that institutions affect Chinese trade flows. In particular, the authors find that China imports more meat products from countries who host qualitatively better institutions and are geographically closer, and that the country’s imports rise with its GDP level. This confirms our hypothesis that institutions in the exporting country are positively associated with meat exports to China.Originality/valueThe importance of the exporters’ institutions for Chinese meat imports has not been studied so far and is of great interest given China’s rising role as a sizable importer. Furthermore, Chinese meat imports have attracted much attention recently due to the country’s potentially significant impact on world food security and sustainable development. Hence, this paper aims to make a substantial contribution to the literature, both from a scientific and a policy perspective.
Why multinational enterprises may be causing more inequality than we think
Authors: Giuliani Elisa 
Published: December 2018

Purpose
This paper aims to discuss the ways in which multinational enterprises (MNEs) may contribute to growing inequality.

Design/methodology/approach
By showing some macroscopic evidence of business-related human rights infringements, this paper claims that the negative impacts of MNEs has been largely overlooked.

Findings
The extent to which MNEs contribute to income-based inequality through the abnormal accumulation of wealth by chief executive officers (CEOs), top managers and shareholders is known, and almost nothing is known about whether this is connected to MNEs’ track record of human rights infringements.

Originality/value
This paper suggest that there might be a connection between MNEs’ human rights infringements and the abnormal accumulation of wealth by companies’ CEOs, top managers and shareholders. It calls for more international business research investigating this link.