bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crime, Intimidation, and Whistleblowing: A Theory of Inference from Unverifiable Reports
Authors: Chassang Sylvain , Miquel Gerard Padró I 
Published: December 2018

AbstractWe consider a game between a principal, an agent, and a monitor in which the principal would like to rely on messages by the monitor (the potential whistleblower) to target intervention against a misbehaving agent. The difficulty is that the agent can credibly threaten to retaliate against the monitor in the event of an intervention. In this setting, intervention policies that are responsive to the monitor’s message provide informative signals to the agent, which can be used to target threats efficiently. Principals that are too responsive to information shut down communication channels. Successful intervention policies must therefore garble the information provided by monitors and cannot be fully responsive. We show that policy evaluation on the basis of non-verifiable whistleblower messages is feasible under arbitrary incomplete information provided policy design takes into account that messages are endogenous.
Ethics Committees
Authors: McCarty Catherine A. , Barnes Robert , Thomas Monica , Sande Jonathan , Ouellette Annette 
Published: December 2018

ABSTRACT:
Healthcare ethics committees can be valuable resources but are largely underutilized by nurses. The purpose of this project was to review ethics concerns and educational needs of nurses in a large, integrated healthcare delivery system. Seven themes were identified: organizational issues, nonbeneficial care, withdrawing life-sustaining therapies, discharge disposition, challenging patients and families, communication with physicians, and capacity versus competence. A process was then developed to better engage nurses in ethical discussions.
Management of Surgical Incisions Using Incisional Negative-Pressure Therapy
Authors: Schlosser Kathryn A. , Otero Javier , Lincourt Amy , Augenstein Vedra A. 
Published: December 2018

Summary:
Use of negative-pressure therapy (NPT) is a well-established therapy for chronic, open, contaminated wounds, promoting formation of granulation tissue and healing. The application of NPT after primary closure (ie, incisional NPT) has also been shown to reduce surgical site infection and surgical site occurrence in high-risk procedures across multiple disciplines. Incisional NPT is believed to decrease edema and shear stress, promote angiogenesis and lymphatic drainage, and increase vascular flow and scar formation. Incisional NPT may be considered when there is a high risk of surgical site occurrence or surgical site infection, particularly in procedures with nonautologous implants, such as hernia mesh or other permanent prosthetics. Here we discuss the proposed physiologic mechanism as demonstrated in animal models and review clinical outcomes across multiple specialties.
Management of Closed Incisions Using Negative-Pressure Wound Therapy in Orthopedic Surgery
Authors: Agarwal Animesh 
Published: December 2018

Summary:
Negative-pressure wound therapy (NPWT) has been a major advance in the management of open wounds, especially in orthopedic trauma surgery. Due to the success of NPWT, surgeons began using NPWT on closed incisions as a way to help prevent surgical wound dehiscence, especially in at-risk patients for wound problems. It has been well established that obesity, diabetes mellitus, and smoking in addition to other comorbidities increase the risk of wound dehiscence and surgical site infections in orthopedic patients. This article reviews the current literature and provides an overview on the use of NPWT on closed incisions in orthopedic trauma procedures and joint arthroplasty.
Transcriptional activation of DBP by hnRNP K facilitates circadian rhythm
Authors: Kwon Paul Kwangho , Lee Kyung-Ha , Kim Ji-hyung , Tae Sookil , Ham Seokjin , Kim Hyo-Min , Choi Jung-Hyun , Jeong Young-Hun , Kim Sung Wook , Yi Hee , Ku Hyun-Ok , Roh Tae-Young , Lim Chunghun , Kim Kyong-Tai 
Published: December 2018

AbstractD-site albumin promoter binding protein (DBP) supports the rhythmic transcription of downstream genes, in part by displaying high-amplitude cycling of its own transcripts compared to other circadian clock genes. However, the underlying mechanism remains elusive. Here, we demonstrated that poly(C) motif within DBP proximal promoters, in addition to an E-box element, provoked the transcriptional activation through increased RNA polymerase 2 (Pol2) recruitment by inducing higher chromatin accessibility. We also clarified that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that binds to the poly(C) motif on single-stranded DNAs in vitro. Chromatin immunoprecipitation further confirmed the expression-dependent and rhythmic binding of hnRNP K which was inhibited through its cytosolic localization mediated by time-dependent ERK activation. Knockdown of hnRNP K triggered low-amplitude mRNA rhythms in DBP and other core clock genes through transcriptional or post-transcriptional regulation. Finally, transgenic depletion of aDrosophilahomolog of hnRNP K in circadian pacemaker neurons lengthened 24-hour periodicity in free-running locomotor behaviors. Taken together, our results provide new insights into the function of hnRNP K as a transcriptional amplifier of DBP, which acts rhythmically through its intracellular localization by the ERK phosphorylation and as an mRNA stabilizer along with its physiological significance in circadian rhythms ofDrosophila.Significance StatementIn the case of mood disorders and the aging process, the mRNA expression and amplitude level of clock genes, including DBP, were reported to be diminished. However, the reason behind this decrease of clock gene amplitude and expression level remained unclear. Through this study, we revealed the regulatory mechanism behind the expression of clock genes, especially of DBP mRNA expression. In addition, we discovered that hnRNP K regulates more core clock genes than what we have previously known, such as Clock and Periods. Finally, we demonstrated the physiological significance of hnRNP K in Drosophila through its RNAi line model. Hence, our findings show the regulatory mechanism of circadian rhythm that may provide insight on mood disorder and aging process.
Long-range single-molecule mapping of chromatin accessibility in eukaryotes
Authors: Shipony Zohar , Marinov Georgi K. , Swaffer Matthew P. , Sinott-Armstrong Nasa A. , Skotheim Jan M. , Kundaje Anshul , Greenleaf William J. 
Published: December 2018

AbstractActive regulatory elements in eukaryotes are typically characterized by an open, nucleosome-depleted chromatin structure; mapping areas of open chromatin has accordingly emerged as a widely used tool in the arsenal of modern functional genomics. However, existing approaches for profiling chromatin accessibility are limited by their reliance on DNA fragmentation and short read sequencing, which leaves them unable to provide information about the state of chromatin on larger scales or reveal coordination between the chromatin state of individual distal regulatory elements. To address these limitations, we have developed a method for profiling accessibility of individual chromatin fibers at multi-kilobase length scale (SMAC-seq, or Single-Molecule long-read Accessible Chromatin mapping sequencing assay), enabling the simultaneous, high-resolution, single-molecule assessment of the chromatin state of distal genomic elements. Our strategy is based on combining the preferential methylation of open chromatin regions by DNA methyltransferases (CpG and GpC 5-methylcytosine (5mC) and N6-methyladenosine (m6A) enzymes) and the ability of long-read single-molecule nanopore sequencing to directly read out the methylation state of individual DNA bases. Applying SMAC-seq to the budding yeast Saccharomyces cerevisiae, we demonstrate that aggregate SMAC-seq signals match bulk-level accessibility measurements, observe single-molecule protection footprints of nucleosomes and transcription factors, and quantify the correlation between the chromatin states of distal genomic elements.
Higher-order epistatic networks underlie the evolutionary fitness landscape of a xenobiotic-degrading enzyme
Authors: Yang Gloria , Anderson Dave W , Baier Florian , Dohmen Elias , Hong Nansook , Carr Paul D , Kamerlin Shina Caroline Lynn , Jackson Colin J , Bornberg-Bauer Erich , Tokuriki Nobuhiko 
Published: December 2018

AbstractCharacterizing the adaptive landscapes that encompass the emergence of novel enzyme functions can provide molecular insights into both enzymatic and evolutionary mechanisms. Here, we combine ancestral protein reconstruction with biochemical, structural, and mutational analyses to characterize the functional evolution of methyl-parathion hydrolase (MPH), a xenobiotic organophosphate-degrading enzyme. We identify five mutations that are necessary and sufficient for the evolution of MPH from an ancestral dihydrocoumarin hydrolase. In-depth analyses of the adaptive landscapes encompassing this evolutionary transition revealed that a complex interaction network, defined in part by higher-order epistasis, determined the adaptive pathways that were available. By also characterizing the adaptive landscapes in terms of their functional activity towards three other OP substrates, we reveal that subtle differences in substrate substituents drastically alter the enzyme’s epistatic network by changing its intramolecular interactions. Our work suggests that the mutations function collectively to enable substrate recognition via subtle structural repositioning.
Microcapsuled entomopathogenic fungus against fire ants
Authors: Qiu Hua-Long , Fox Eduardo G P , Zhao Dan-Yang , Xu Jin-Zhu , Qin Chang-Sheng 
Published: December 2018

AbstractA new microencapsulation method of Metarhizium anisopliae based on gelatin (GE) and gum arabic (GA) is presented. Conditions to produce spheres 35-50 μm relied on 1% wall material, GE:GA ratio 1:1–1:2, core:wall ratio 1:1, under pH 4.0, 35-50°C and 500-700 r/min agitation. Microcapsulation provided protection against UV and longer shelf life as compared to unencapsulated conidia. The obtained preparation proved active against the red imported fire ant Solenopsis invicta.
Systems-level network modeling of Small Cell Lung Cancer subtypes identifies master regulators and destabilizers
Authors: Wooten DJ , Maddox SF , Tyson DR , Liu Q , Lim JS , Lopez CF , Sage J , Quaranta V 
Published: December 2018

AbstractAdopting a systems approach, we devise a general workflow to define actionable subtypes in human cancers. Applied to small cell lung cancer (SCLC), the workflow identifies four subtypes based on global gene expression patterns and ontologies. Three correspond to known subtypes, while the fourth is a previously undescribed neuroendocrine variant (NEv2). Tumor deconvolution with subtype gene signatures shows that all of the subtypes are detectable in varying proportions in human and mouse tumors. To understand how multiple stable subtypes can arise within a tumor, we infer a network of transcription factors and develop BooleaBayes, a minimally-constrained Boolean rule-fitting approach.In silicoperturbations of the network identify master regulators and destabilizers of its attractors. Specific to NEv2, BooleaBayes predicts ELF3 and NR0B1 as master regulators of the subtype, and TCF3 as a master destabilizer. Since the four subtypes exhibit differential drug sensitivity, with NEv2 consistently least sensitive, these findings may lead to actionable therapeutic strategies that consider SCLC intratumoral heterogeneity. Our systems-level approach should generalize to other cancer types.
Cytoplasmic self-organization established by internal lipid membranes in the interplay with either actin or microtubules
Authors: Tang Sindy K. Y. , Renz Malte , Shemesh Tom , Driscoll Meghan , Lippincott-Schwartz Jennifer 
Published: December 2018

AbstractCells harbor an intrinsic organization of their components. Specific protein structures, as the centrosome, have been described master regulators of cell organization. In the absence of these key elements, however, cytoplasmic selforganization has nevertheless been observed. Cytoplasmic self-organization was postulated to arise from the interaction of microtubules with molecular motors on lipid membrane surfaces.Here, we show that lipid membranes are capable of organizing both major cytoskeletal systems, microtubules and actin, even if one or the other cytoskeletal system is completely paralyzed. A microfluidic droplet system and Xenopus oocyte extracts enabled us to build an artificial cell and study minimal requirements for cellular self-organization. Mathematical modeling reveals the interaction of lipid membranes with any filament system through molecular motors as a universal principle of cytoplasmic self-organization. Both cytoskeletal systems form mechanisms to establish robust 2-dimensional selforganization and self-centering. Pharmacologic inhibition of the cytoskeletal network systems helps dissect specific contributions of each network in the interplay with lipid membranes with regards to 2- and 3-dimensional organization, time and length scale of cytoplasmic organization and the degree of concentration of the centered elements. While microtubules provide 3-dimensional polarity, actin filaments ensure fast and dense compaction and long-range organization.
Interactions between non-structured domains of FG- and non-FG-nucleoporins coordinate the ordered assembly of the nuclear pore complex in mitosis
Authors: Konishi Hide A. , Yoshimura Shige H. 
Published: December 2018

SummaryIn this study, we examined how channel-forming subunits of the nuclear pore complex (NPC) are assembled into a selective channel within a highly structured scaffold ring during post-mitotic assembly. We focused on non-structured domains of the scaffold Nups and performed in vitro self-assembled particle assays with those derived from channel-forming FG-Nups. We found that non-structured domains of ELYS and Nup35N interacted with channel-forming FG-Nups to form a self-assembled particle. Sequential addition of FG-Nups into the scaffold particle revealed that ELYS, which initiates post-mitotic NPC reassembly, interacts with early assembling FG-Nups (Nups98 and 153) but not middle stage-assembling FG-Nups (Nups58 and 62). Nup35, which assembles between the early and middle stages, facilitated the assembly of Nup62 into the early assembling Nups both in vitro and in vivo. These results demonstrate that ELYS and Nup35 have a role of facilitator in the ordered assembly of channel-forming FG-Nups during mitosis.
Postural adjustments in anticipation of predictable perturbations allow elderly fallers to achieve a balance recovery performance equivalent to elderly non-fallers
Authors: Le Mouel Charlotte , Tisserand Romain , Robert Thomas , Brette Romain 
Published: December 2018

AbstractBackgroundIn numerous laboratory-based perturbation experiments, differences in the balance recovery performance of elderly fallers and non-fallers are moderate or absent. This performance may be affected by the subjects adjusting their initial posture in anticipation of the perturbation.Research questionsDo elderly fallers and non-fallers adjust their posture in anticipation of externally-imposed perturbations in a laboratory setting? How does this impact their balance recovery performance?Methods21 elderly non-fallers, 18 age-matched elderly fallers and 11 young adults performed both a forward waist-pull perturbation task and a Choice Stepping Reaction Time (CSRT) task. Whole-body kinematics and ground reaction forces were recorded. For each group, we evaluated the balance recovery performance in the perturbation task, change in initial center of mass (CoM) position between the CSRT and the perturbation task, and the influence of initial CoM position on task performance.ResultsThe balance recovery performance of elderly fallers was equivalent to elderly non-fallers (p > 0.5 Kolmogorov-Smirnov test). All subject groups anticipated forward perturbations by shifting their CoM backward compared to the CSRT task (young: 2.1% of lower limb length, elderly non-fallers: 2.7%, elderly fallers: 2.2%, Hodges-Lehmann estimator, p < 0.001 Mann-Whitney U). This backward shift increases the probability of resisting the traction without taking a step.SignificanceThe ability to anticipate perturbations is preserved in elderly fallers and may explain their preserved balance recovery performance in laboratory-based perturbation tasks. Therefore, future fall risk prediction studies should carefully control for this postural strategy, by interleaving perturbations of different directions for example.
Complete genome sequence of a divergent strain of Tibetan frog hepatitis B virus associated to concave-eared torrent frogOdorrana tormota
Authors: Debat Humberto J. , Ng Terry Fei Fan 
Published: December 2018

AbstractThe familyHepadnaviridaeis characterized by partially dsDNA circular viruses of approximately 3.2 kb, which are reverse transcribed from RNA intermediates. Hepadnaviruses (HBVs) have a broad host range which includes humans (Hepatitis B virus), other mammals (genusOrthohepadnavirus), and birds (Avihepadnavirus). HBVs host specificity has been expanded by reports of new viruses infecting fish, amphibians, and reptiles. The tibetan frog hepatitis B virus (TFHBV) was recently discovered inNanorana parkeri(FamilyDicroglossidae) from Tibet. To increase understanding of hepadnavirus in amphibian host, we identified the full-length genome of a divergent strain TFHBV-Ot associated to the concave-eared torrent frogOdorrana tormota(FamilyRanidae) from China by searching deep sequencing data. TFHBV-Ot shared the genomic organization and a 76.6% overall genome nucleotide identity to the prototype TFHBV associated toN. parkeri(TFHBV-Np). TFHBV-Ot amino acid pairwise identity with TFHBV-Np predicted gene products ranged between 63.9% and 77.9%. Multiple tissue/organ specific RNAseq datasets suggest a broad tropism of TFHBV including muscles, gonads and brains. In addition, we provide for the first time evidence of virus derived small RNA from an amphibian hepadnavirus, tentatively enriched in 19-20 nt species and cytidine as first base. The results presented here expand the genetic diversity and the host range of TFHBV toRanidaefrogs, and warrant investigation on hepadnaviral infection of amphibian brains.
Chromomycin, an antibiotic produced by Streptomyces flaviscleroticus might play a role in the resistance to oxidative stress and is essential for viability in stationary phase
Authors: Prajapati Divya , Kumari Namita , Dave Keyur , Chatupale Vaidehi , Pohnerkar Jayashree 
Published: December 2018

SummaryThe well‐known role of antibiotics in killing sensitive organisms has been challenged by the effects they exert at subinhibitory concentrations. Unfortunately, there are very few published reports on the advantages these molecules may confer to their producers. This study describes the construction of a genetically verified deletion mutant of Streptomyces flaviscleroticus unable to synthesize chromomycin. This mutant was characterized by a rapid loss of viability in stationary phase that was correlated with high oxidative stress and altered antioxidant defences. Altered levels of key metabolites in the mutant signalled a redistribution of the glycolytic flux toward the PPP to generate NADPH to fight oxidative stress as well as reduction of ATP‐phosphofructokinase and Krebs cycle enzymes activities. These changes were correlated with a shift in the preference for carbon utilization from glucose to amino acids. Remarkably, chromomycin at subinhibitory concentration increased longevity of the non‐producer and restored most of the phenotypic features’ characteristic of the wild type strain. Altogether these observations suggest that chromomycin may have antioxidant properties that would explain, at least in part, some of the phenotypes of the mutant. Our observations warrant reconsideration of the secondary metabolite definition and raise the possibility of crucial roles for their producers.
Evaluation of monosodium iodoacetate dosage to induce knee osteoarthritis: Relation with oxidative stress and pain
Authors: Yamada Eloá Ferreira , Salgueiro Andréia Fernandes , Goulart Aline da Silva , Mendes Vanessa Pereira , Anjos Bruno Leite , Folmer Vanderlei , da Silva Morgana Duarte 
Published: December 2018

AbstractAimTo determine the dose of monosodium iodoacetate (MIA) required to induce oxidative stress, as well as pain and edema; to confirm the induction of knee osteoarthritis (OA) symptoms in rats by the presence of reactive oxygen species (ROS) and reduction of antioxidant agents; and to verify the presence of histopathological injury in these affected joints.MethodBiological markers of oxidative stress, pain, knee edema, and cartilage degeneration provided by different doses of MIA (0.5; 1.0 or 1.5 mg) in rat knee joints were analyzed. The animal evaluations were conducted during 15 days for mechanical and cold hypersensitivity, spontaneous pain and edema. After that, blood serum, intra‐articular lavage and structures of knee, spinal cord and brainstem were collected for biochemical analysis; moreover, the knees were removed for histological evaluation.ResultsThis study demonstrates that the highest dose of MIA (1.5 mg) increased the oxidative stress markers and reduced the antioxidant reactions, both in the focus of the lesion and in distant sites. MIA also induced the inflammatory process, characterized by pain, edema, increase in neutrophil count and articular damage.ConclusionThis model provides a basis for the exploration of underlying mechanisms in OA and the identification of mechanisms that may guide therapy and the discovery of OA signals and symptoms.
Liana abundance and relationships to sapling and tree hosts in an East African primary forest
Authors: Laurentino Telma G. , Baur Julian , Usui Takuji , Eichhorn Markus P. 
Published: December 2018

AbstractLianas are an important structural component of tropical rain forests. Recent concern regarding a putative global rise in liana abundance, and its implications for forest conservation, calls for data collection across biomes. We here provide a first assessment and baseline data for a geographical gap in liana surveys to date. We surveyed liana (diameter at breast height [DBH] > 1 cm), tree (DBH > 10 cm) and sapling (DBH ≤ 10 cm) abundance and basal area, as well as liana–host relationships, in a tropical East African primary forest. We recorded a total of 347 liana stems (DBH > 1 cm) in 0.31 ha, with an average basal area of 1.21 m2/ha. Lianas were found to be widespread, with 24% of saplings and 57% of trees colonised by at least one liana, independently of bark texture or host diameter. The dominant liana colonisation strategy was to associate with a single host, through stem twining. We found no evidence of liana density being influenced by host density. We synthesised published liana density data across continents and report that our estimate of liana density for Kibale's primary forest fits within the expected range of liana densities for primary tropical forests. This synthesis further highlights a neotropical sampling bias, which our findings make a step towards addressing.