bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational assessment of blood flow heterogeneity in dialysis patients’ cardiac ventricles
Authors: Kharche Sanjay R , So Aaron , Salerno Fabio , Lee Ting-Yim , Ellis Chris , Goldman Daniel , McIntyre C W 
Published: April 2018

AbstractDialysis prolongs life but augments cardiovascular mortality. Imaging data suggests that dialysis increases myocardial blood flow (BF) heterogeneity, but its causes remain poorly understood. A biophysical model of human coronary vasculature was used to explain the imaging observations, and highlight causes of coronary BF heterogeneity.Post-dialysis CT images from patients under control, pharmacological stress (adenosine), therapy (cooled dialysate), and adenosine and cooled dialysate conditions were obtained. The data presented disparate phenotypes. To dissect vascular mechanisms, a 3D human coronary vasculature model was implemented. Simulations were performed to investigate the effects of altered aortic pressure and blood vessel diameters on myocardial BF heterogeneity which was quantified using relative dispersion, fractal dimension, and transmural BF distribution.Imaging showed that stress and therapy potentially increased mean and total BF, while reducing heterogeneity. BF histograms of one patient showed multi-modality. Using the model, it was found that total coronary BF increased as coronary perfusion pressure (CPP) was increased. BF heterogeneity was differentially affected by large or small vessel blocking. BF heterogeneity was found to be inversely related to small blood vessel diameters. Simulation of large artery stenosis indicates that BF became heterogeneous (increase relative dispersion) and gave multi-modal histograms. The total transmural BF as well as transmural BF heterogeneity reduced due to large artery stenosis, generating large patches of very low BF regions downstream. Blocking of arteries at various orders showed that blocking larger arteries results in multi-modal BF histograms and large patches of low BF, whereas smaller artery blocking results in augmented relative dispersion and fractal dimension. Transmural heterogeneity was also affected. Finally, the effects of augmented aortic pressure in the presence of blood vessel blocking shows differential effects on BF heterogeneity as well as transmural BF.Improved aortic blood pressure may lead to improved BF. Stress and therapy may be effective if they dilate small vessels. A potential cause for the observed complex BF distributions (multi-modal BF histograms) may indicate existing large vessel stenosis.The intuitive BF heterogeneity methods used can be readily used in clinical studies. Further development of the model and methods will permit personalised assessment of patient BF status.
A population-based human enCYCLOPedia for circadian medicine
Authors: Ruben Marc D. , Wu Gang , Smith David F. , Schmidt Robert E. , Francey Lauren J. , Anafi Ron C. , Hogenesch John B. 
Published: April 2018

AbstractThe discovery that half of the mammalian protein-coding genome is clock-regulated has clear implications for medicine. Indeed, recent studies demonstrate time-of-day impact on therapeutic outcomes in human heart disease and cancer. Yet biological time is rarely given clinical consideration. A key barrier is the absence of information on thewhatandwhereof molecular rhythms in the human body. Here, we have applied CYCLOPS, an algorithm designed to reconstruct sample order in the absence of time-of-day information, to the GTEx collection of 632 human donors contributing 4,292 RNA-seq samples from 13 distinct human tissue types. We identify rhythms in expression across the body that persist at the population-level. This includes a set of ‘ubiquitous cyclers’ comprised of well-established circadian clock factors but also many genes without prior circadian context. Among thousands of tissue-divergent rhythms, we discover a set of genes robustly oscillating in cardiovascular tissue, including key drug targets relevant to heart disease. These results also have implications for genetic studies where circadian variability may have masked genetic influence. It is our hope that the human enCYCLOPedia helps drive the translation of circadian biology into prospective clinical trials in cardiology and many other therapeutic areas.One Sentence SummaryBioinformatic analyses on thousands of human tissue samples reveals an enCYCLOPedia of rhythmic gene expression across the body and identifies key translational opportunities for circadian medicine in cardiovascular disease.
The polar localization hub protein PopZ restrains adaptor dependent ClpXP proteolysis inCaulobacter crescentus
Authors: Joshi Kamal Kishore , Chien Peter 
Published: April 2018

ABSTRACTInCaulobacter crescentus, timely degradation of several proteins by the ClpXP protease is critical for proper cell cycle progression. During the cell cycle, the ClpXP protease, the substrate CtrA and many other proteins are localized to the stalked pole dependent on a polar interaction hub composed of PopZ protein oligomers. Prior work suggests that the localization of ClpXP, protease substrates, and cofactors is needed for recognition of substrates such as CtrA by ClpXP. Here, we formally test this hypothesis by examining the role of PopZ in ClpXP activity and find surprisingly that CtrA degradation is enhanced in cells lacking polar localization due to loss of PopZ. The ClpXP adaptor CpdR is required for this enhanced degradation of CtrA and other adaptor-dependent substrates, but adaptor-independent substrate degradation is not affected upon loss of PopZ. We find that overexpression of PopZ also leads to faster degradation of CtrA, but is likely due to nonphysiologically relevant recognition of CtrA by ClpXP alone as loss of CpdR does not affect this enhancement. Our main conclusion is that loss of PopZ, and therefore loss of polar localization, does not result in the loss of ClpXP regulated proteolysis, as would be predicted from a model which requires polar localization of ClpXP for its activation. Rather, our data point to a model where PopZ normally restrains ClpXP proteolysis by promoting the inactivation of the CpdR adaptor, likely through the phosphorylation activity of the CckA kinase.
Computational assessment of arrhythmia potential in the heterogeneously perfused ventricle
Authors: Kharche Sanjay R , McIntyre Christopher W 
Published: April 2018

AbstractBackgroundThe heterogeneity in the human left ventricle is augmented by heterogeneous perfusion defects in dialysis patients. We hypothesized that ischemic zones generated by heterogeneous perfusion are a cause of clinically observed post-dialysis arrhythmia. This preliminary study assessed the arrhythmia potential in a heterogeneously perfused 2D human ventricle computational model.AimOur aim was to ascertain a relationship between the number of ischemia zones and incidence of multiple re-entrant waves in a 2D model of the human ventricle.MethodsA human ventricle action potential model was modified to include the adenosine triphosphate (ATP) sensitive potassium current. Within ischemic zones, cell electrophysiological alterations due to ischemia were implemented as increased extracellular potassium, reduced intracellular ATP concentrations, as well as reduced upstroke current conductances. The cell model was incorporated into a spatial 2D model. The inter-cellular gap junction coupling was adjusted to simulate slow conduction in dialysis patient hearts. CT imaging data of the heart obtained during dialysis was analysed to estimate the approximate spatial size of ischemic zones. An ischemic border zone between the normal and central ischemic zones was implemented which had smoothly varying electrophysiological parameters. Arrhythmic potential was assessed using the paths of the centres of the re-entrant waves, called tip trajectories, and dominant frequency maps.ResultsExtracellular potassium elevated the resting potential and IKATP reduced the action potential’s duration. In the absence of ischemic zones, the propensity of the model to induce multiple re-entrant waves was low. The inclusion of ischemic zones provided the substrate for initiation of re-entrant wave fibrillation. The dominant frequency which measured the highest rate of pacing in the tissue increased drastically with the inclusion of ischemic zones, going from 3 Hz in the pre-dialysis state to over 6 Hz in the post-dialysis state. Re-entrant wave tip numbers increased from 1 tip in the pre-dialysis case to 34 in the post-dialysis case, a 34 fold increase. The increase of tip number was found to be strongly correlated to tissue heterogeneity in terms of ischemic zone numbers. Computational factors limiting a more extensive simulation of cause-effect combinations were identified.ConclusionsA dialysis session restores systemic homeostasis, but promotes deleterious arrhythmias. Structure-function mechanistic modelling will permit patient-specific assessment of health status. Such an effort is expected to lead to application of wider physical sciences methods in the improvement of the lives of critically ill patients. High performance computing is a crucial requirement for such mechanistic assessment of health status.
Evolved sequence features within the intrinsically disordered tail influence FtsZ assembly and bacterial cell division
Authors: Cohan Megan C. , Posey Ammon E. , Grigsby Steven J. , Mittal Anuradha , Holehouse Alex S. , Buske Paul J. , Levin Petra A. , Pappu Rohit V. 
Published: April 2018

AbstractIntrinsically disordered regions (IDRs) challenge the well-established sequence-structure-function paradigm for describing protein function and evolution. Here, we direct a combination of biophysical and cellular studies to further our understanding of how the intrinsically disordered C-terminal tail of FtsZ contributes to cell division in rod-shaped bacteria. FtsZ is a modular protein that encompasses a conserved GTPase domain and a highly variable intrinsically disordered C-terminal tail (CTT). The CTT is essential for forming the cytokinetic Z-ring. Despite poor sequence conservation of the CTT, the patterning of oppositely charged residues, which refers to the extent of linear mixing / segregation of oppositely charged residues within CTT sequences is bounded within a narrow range. To assess the impact of evolutionary bounds on charge patterning within CTT sequences we performed experiments, aided by sequence design, to quantify the impact of changing the patterning of oppositely charged residues within the CTT on the functions of FtsZ from B. subtilis. Z-ring formation is robust if and only if the extent of linear mixing / segregation of oppositely charged residues within the CTT sequences is within evolutionarily observed bounds. Otherwise, aberrant, CTT-mediated, FtsZ assemblies impair Z-ring formation. The complexities of CTT sequences also have to be above a threshold value because FtsZ variants with low complexity CTTs are not tolerated in cells. Taken together, our results suggest that CTT sequences have evolved to be “just right” and that this is achieved through an optimal extent of charge patterning while maintaining the sequence complexity above a threshold value.
A zero percent plastic ingestion rate by silver hake (Merluccius bilinearis) from the south coast of Newfoundland, Canada
Authors: Liboiron France , Ammendolia Justine , Saturno Jacquelyn , Melvin Jessica , Zahara Alex , Richárd Natalie , Liboiron Max 
Published: April 2018

AbstractSilver hake, (Merluccius bilinearis), contributes significant biomass to Northwest Atlantic ecosystems. The incidence of plastic ingestion for 134 individuals collected from Newfoundland, Canada was examined through visual examination of gastrointestinal contents and Raman spectrometry. We found a frequency of occurrence of ingestion of 0%. Through a comprehensive literature review of globally published fish ingestion studies, we found our value to be consistent with 41% (n=100) of all reported fish ingestion rates. We could not statistically compare silver hake results to other species due to low sample sizes in other studies (less thann=20) and a lack of standardized sampling methods. We recommend that further studies should 1) continue to report 0% plastic ingestion rates and 2) should describe location and species-specific traits that may contribute to 0% ingestion rates, particularly in locations where fish consumption has cultural and economic significance.
Lon recognition of the replication initiator DnaA is not confined to a single degron
Authors: Liu Jing , Francis Laura , Chien Peter 
Published: April 2018

SummaryDnaA initiates chromosome replication in bacteria. InCaulobacter crescentus, the Lon protease degrades DnaA to coordinate replication with nutrient availability and to halt the cell cycle during acute stress. Here we characterize the mechanism of DnaA recognition by Lon. We find that the native folded state of DnaA is crucial for its degradation, in contrast to the well-known role of Lon in degrading misfolded proteins. We fail to identify a single degradation motif (degron) sufficient for DnaA degradation, rather we show that both the ATPase domain and a species-specific N-terminal motif are important for productive Lon degradation of DnaA. Mutations in either of these determinants disrupt DnaA degradationin vitroandin vivo.DnaA switches from an inactive to active state depending on its nucleotide state and we find that locking DnaA in an active state inhibits degradation. Our working model is that Lon engages DnaA through at least two elements, one of which anchors DnaA to Lon and the other acting as an initiation site for degradation.
Alteration of serum thymus and activation‐regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti‐interleukin‐17A agents
Authors: Shibuya Takashi , Honma Masaru , Iinuma Shin , Iwasaki Takeshi , Takahashi Hidetoshi , Ishida‐Yamamoto Akemi 
Published: April 2018

AbstractBiologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side‐effects of biologics, dose‐reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation‐regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI‐clear with biologics than in the group which did not achieve PASI‐clear. Among biologics, the group treated with secukinumab, an anti‐interleukin (IL)‐17A agent, showed significantly higher TARC level compared with the group treated with anti‐tumor necrosis factor agents. In certain populations achieving PASI‐clear, serum TARC level may be a potent marker reflecting better response to IL‐17A inhibitors, and in this case step down of treatment for psoriasis is possible.
Successful treatment with interleukin‐17A antagonists of generalized pustular psoriasis in patients without IL36RN mutations
Authors: Wilsmann‐Theis Dagmar , Schnell Lisa Marie , Ralser‐Isselstein Veronika , Bieber Thomas , Schön Michael P. , Hüffmeier Ulrike , Mössner Rotraut 
Published: April 2018

AbstractGeneralized pustular psoriasis (GPP) is a potentially life‐threatening disease that can be attributed to mutations in IL36RN in a subgroup of patients. In small trials, interleukin (IL)‐17A and IL‐17RA antagonists have been shown to be effective in patients with generalized pustular psoriasis in Japan. We identified seven patients who received the IL‐17A antagonists secukinumab (six cases) or ixekizumab (one case) in two dermatological centers. All patients showed a good or excellent clinical response. Anti‐IL‐17A therapy was well tolerated and ongoing in all patients after an average therapy duration of 12.9 months. Analysis of IL36RN mutation status was performed in six patients, one patient carried a heterozygous mutation, while the other five patients did not show a mutation in IL36RN. This is the first report of a successful treatment of GPP patients without IL36RN mutations responding to anti‐IL‐17A therapy.
Bone marrow ‐ mesenchymal stem cells impact on the U937 cells in the presence of staphylococcal enterotoxin B (SEB)
Authors: Ejtehadifar Mostafa , Halabian Raheleh , Ghazavi Ali , Khansarinejad Behzad , Mosayebi Ghasem , Imani Fooladi Abbas Ali 
Published: April 2018

SummaryThe growing resistance against conventional chemotherapy in acute myeloid leukemia (AML) is a noticeable clinical concern. Therefore, many researchers are looking for novel substances to overcome drug resistance in cancer. Staphylococcal enterotoxin B (SEB) is a superantigen (SAg) and a promising compound which has lethal effects on malignant cells. In this unprecedented study, SEB was used against U937 cells in a co‐culture system in the presence of human bone marrow‐mesenchymal stem cells (hBM‐MSCs). The effects of hBM‐MSCs on the proliferation and survival of U937 cell line with SEB was assessed using MTT assay and AnnexinV/PI flowcytometry, respectively. Moreover, the expression of IL‐6, IL‐10, TGF‐β, and inhibitor of nuclear factor kappa‐B kinase (IKKb) was evaluated by real‐time PCR technique. The same experiments were also carried out using hBM‐MSCs‐conditioned medium (hBM‐MSCs‐CM). The results showed that SEB reduced the proliferation and survival of U937 cell line, but hBM‐MSCs or hBM‐MSCs‐CM suppressed the effects of SEB. Furthermore, real‐timePCR demonstrated that SEB could decrease the expression of IL‐6, IL‐10, and TGF‐β in hBM‐MSCs (P < .05), while the production of IKKb was increased in comparison with the control group. These findings help us to have a broader understanding ofthe usage of SEB in the treatment of haematological malignancies, especially if it is targeted against hBM‐MSCs to disrupt their supportive effects on malignant cells.
The role of interleukin‐4 in rheumatic diseases
Authors: Dong Chen , Fu Ting , Ji Juan , Li Zhenyu , Gu Zhifeng 
Published: April 2018

SummaryRheumatism is a group of diseases, most of which are autoimmune diseases, that violate joints, bones, muscles, blood vessels and related soft tissue. As is well known, cytokines play a role in the pathogenesis of several rheumatic diseases, such as rheumatoid arthritis, spondyloarthritides, and systemic lupus erythematosus. Recently, the role of interleukin‐4 (IL‐4), which may participate in the mechanism of rheumatism, have been discovered. It is reported that IL‐4 takes part in the regulation of T cell activation, differentiation, proliferation, and survival of different T cell types. IL‐4 also has an immunomodulatory effect on B cells, mast cells, macrophages, and many cell types. A review of the literature on functions of IL‐4 in rheumatic diseases is presented.
Avian preparedness: simulations of bird diseases and reverse scenarios of extinction in Hong Kong, Taiwan, and Singapore
Authors: Keck Frédéric 
Published: April 2018

AbstractThis article describes relations between humans, animals, artefacts, and pathogens in simulations of disasters, taking bird diseases in three Chinese sentinel posts as ethnographic cases. Drawing on distinctions between simulation, ritual, and play, it shows that the engagement of actors in the imaginary of simulations, which they describe as ‘realism’, reflectively reverses the oppositions between humans and nonhumans, active and passive, fiction and reality that shape ordinary life. Borrowing from the anthropology of hunting societies, it argues that simulations of bird diseases, considered as signs of future species extinction, rely on cynegetic techniques of power, in which humans and animals symmetrically shift perspectives, and not only on pastoralist techniques, in which humans are above the population they monitor and sometimes sacrifice.
‘Music is my AK‐47’: performing resistance in Belfast's rebel music scene
Authors: Millar Stephen R. 
Published: April 2018

AbstractThis article examines how some Irish republicans have used ‘rebel songs’ as a means to resist the hegemonic power of the British state, and how militant republicanism is invoked musically, through sonic and physical references to gunfire. It explores how the use of rebel songs has changed, the inherent tensions within today's scene, and how republicans attempt to co‐opt other conflicts as a means to strengthen their claim as resistance fighters. The article also analyses more nuanced resistances within the rebel music scene, exploring how competing republican factions use the same music to express opposing political positions, and why some musicians ultimately leave the scene on account of the musical and political restrictions placed upon them. In so doing, the article connects with ongoing attempts to rethink, remap, and develop new approaches to resistance within anthropology, while contributing to the developing subfield of ‘ethnomusicology in times of trouble’.
Humerus photon starvation streak artefact
Authors: Al‐Ogaili Zeyad , Reed Anita J , Burrage John 
Published: April 2018

AbstractIntroductionThe reduced (attenuated) number of photons passing through the arm can result in a combination of fine and thick streak artefacts, particularly with the use of thin CT slices and lower radiation dose parameters. This phenomenon is known as photon starvation. We noted an abnormal appearance of the humerus when imaged with certain arm position. This appearance was thought to be artefact due to photon starvation.MethodsA human radius bone was imaged in different positions and the kV and mA were varied in an attempt to reproduce the artefact, which would support the hypothesis that the artefact may be caused by bone attenuation.ResultsScanning the bone in a different angle and radiation dose parameters reproduced the artefactual appearance of the bone.ConclusionPerforming a chest CT scan with arms up can occasionally result in an abnormal appearance to the humerus due to photon starvation artefact. Familiarity with this artefact is essential to avoid misinterpretation.
The Strategizing of Policy Entrepreneurs towards the Global Alliance for Climate‐Smart Agriculture
Authors: Faling Marijn , Biesbroek Robbert , Karlsson‐Vinkhuyzen Sylvia 
Published: April 2018

AbstractGlobal collaborations across level, domain, and sector boundaries are on the rise. This article analyses policy entrepreneurship for the establishment of the Global Alliance for Climate‐Smart Agriculture (GACSA), a global multi‐actor collaboration to address climate change and foster food security and development. We explore policy entrepreneurship as a process embedded within specific contexts. To that end we focus on the strategizing process, consisting of conditions, activities, and implications. Through a congruence case study based on interviews, documents, survey, and observation we find that: (1) accommodating a varied global community requires flexibility and adaptability from entrepreneurs towards a dynamic and changing environment; (2) the variety of actors constituting GACSA compromises vigour of the collaboration, and confuses the meaning of CSA; (3) whereas collective entrepreneurship is often depicted as joint operation of multiple actors, it might also be characterized by conflicting activities and/or successive involvement; (4) policy entrepreneurship is useful to establish collaborations, but its role is temporary. Entrepreneurs must therefore be sensitive to their potential obsoleteness and withdraw at the right moment. Our results show that policy entrepreneurship is a useful lens to study global policy processes, while providing guidelines to inspire and support practitioners to engage with global policy processes.