bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of Mannose Binding Lectin in the immune response against Borrelia burgdorferi sensu lato
Authors: Coumou Jeroen , Wagemakers Alex , Narasimhan Sukanya , Schuijt Tim J. , Ersoz Jasmin I. , Oei Anneke , de Boer Onno J. , Roelofs Joris J. T. H. , Fikrig Erol , Hovius Joppe W. 
Published: February 2019

AbstractThe causative agents of Lyme borreliosis, spirochetes belonging to the Borrelia burgdorferi sensu lato group, have developed several ways to protect themselves against killing by the host complement system. In addition, it has been shown that serum sensitive isolates are (partially) protected by the Ixodes Tick Salivary Lectin Pathway Inhibitor (TSLPI) protein; a salivary gland protein that inhibits the function of Mannose Binding Lectin (MBL). MBL is a C-type lectin that recognizes oligosaccharides on pathogens and activates the complement system via the lectin pathway. MBL deficiency has been linked to a more severe course of several infectious diseases and humans with detectable antibodies against B. burgdorferi are significantly more often MBL deficient compared to humans without antibodies against B. burgdorferi. Here we set out to investigate the role of MBL in the immune response against B. burgdorferi in more detail. We demonstrate that B. burgdorferi N40 needle-infected C57BL/6 MBL deficient mice harbored significantly higher B. burgdorferi numbers in skin tissue during the early course of infection. In line with these findings they also developed higher anti-B. burgdorferi IgG serum antibodies compared to WT controls. In contrast, B. burgdorferi loads in distant tissue such as heart, joints or bladder at later time points were similar for both mouse strains. These in vivo findings were corroborated using a B. burgdorferi N40-infected I. scapularis infestation model. We showed that MBL is capable of binding B. burgdorferi through its carbohydrate recognition domains, but in vitro complement killing assays, peritoneal macrophage and whole blood stimulations, phagocytosis assays and an in vivo migration experiment did not reveal the mechanism by which MBL facilitates early clearance of B. burgdorferi. To conclude, we show a protective role of MBL in the early stages of B. burgdorferi infection, yet the underlying mechanism warrants further investigation.
Nitrate and ammonium fluxes to diatoms and dinoflagellates at a single cell level in mixed field communities in the sea
Authors: Olofsson Malin , Robertson Elizabeth K. , Edler Lars , Arneborg Lars , Whitehouse Martin J. , Ploug Helle 
Published: February 2019

AbstractGrowth of large phytoplankton is considered to be diffusion limited at low nutrient concentrations, yet their constraints and contributions to carbon (C) and nitrogen fluxes in field plankton communities are poorly quantified under this condition. Using secondary ion mass spectrometry (SIMS), we quantified cell-specific assimilation rates of C, nitrate, and ammonium in summer communities of large phytoplankton when dissolved inorganic nitrogen concentrations are low in temperate coastal regions. Chain-forming diatoms composed 6% of total particulate organic carbon, but contributed 20% of C assimilation, 54% of nitrate assimilation and 32% of ammonium assimilation within the plankton community. In contrast, large dinoflagellates composed 11% of total POC, and contributed 14% of the C assimilation, 4% of ammonium and 9% of nitrate assimilation within the plankton community. Measured cell-specific C and nitrate assimilation rate match the Redfield ratio and the maximal nitrate assimilation in Chaetoceros spp. predicted by mass transfer theory. However, average ammonium assimilation rates were 30 and 340% higher than predicted by mass transfer theory in Tripos/Ceratium and Chaetoceros, respectively, suggesting that microbial interactions in the phycosphere may facilitate substantial luxury ammonium uptake by Chaetoceros in environments with fluctuating nitrate concentrations.
Microbes Producing L-Asparaginase free of Glutaminase and Urease isolated from Extreme Locations of Antarctic Soil and Moss
Authors: Ashok Anup , Doriya Kruthi , Rao Jyothi Vithal , Qureshi Asif , Tiwari Anoop Kumar , Kumar Devarai Santhosh 
Published: February 2019

AbstractL-Asparaginase (L-asparagine aminohydrolase, E.C. 3.5.1.1) has been proven to be competent in treating Acute Lymphoblastic Leukaemia (ALL), which is widely observed in paediatric and adult groups. Currently, clinical L-Asparaginase formulations are derived from bacterial sources such as Escherichia coli and Erwinia chrysanthemi. These formulations when administered to ALL patients lead to several immunological and hypersensitive reactions. Hence, additional purification steps are required to remove toxicity induced by the amalgamation of other enzymes like glutaminase and urease. Production of L-Asparaginase that is free of glutaminase and urease is a major area of research. In this paper, we report the screening and isolation of fungal species collected from the soil and mosses in the Schirmacher Hills, Dronning Maud Land, Antarctica, that produce L-Asparaginase free of glutaminase and urease. A total of 55 isolates were obtained from 33 environmental samples that were tested by conventional plate techniques using Phenol red and Bromothymol blue as indicators. Among the isolated fungi, 30 isolates showed L-Asparaginase free of glutaminase and urease. The L-Asparaginase producing strain Trichosporon asahii IBBLA1, which showed the highest zone index, was then optimized with a Taguchi design. Optimum enzyme activity of 20.57 U mL−1 was obtained at a temperature of 30 °C and pH of 7.0 after 60 hours. Our work suggests that isolation of fungi from extreme environments such as Antarctica may lead to an important advancement in therapeutic applications with fewer side effects.
Elevated plasma D-dimer levels in dermatomyositis patients with cutaneous manifestations
Authors: Habe Koji , Wada Hideo , Higashiyama Ayaka , Akeda Tomoko , Tsuda Kenshiro , Mori Ryoko , Kakeda Masato , Yamanaka Keiichi , Mizutani Hitoshi 
Published: February 2019

AbstractTo explore the influence of dermatomyositis (DM)-specific cutaneous manifestations (scm) on systemic coagulation and fibrinolysis, we retrospectively studied plasma D-dimer levels with/without venous thromboembolism (VTE), malignancy, infection or other connective tissue diseases (CTDs) and scm. One hundred fifty patients with DM were retrospectively investigated using medical records regarding scm, VTE, malignancy, infection, other CTDs, laboratory data and systemic corticosteroid therapy. All DM patients were categorized as follows: group 1, without scm, VTE, infection, malignancy or other accompanying CTDs; group 2, with scm only; and group 3, with VTE, infection, malignancy and other accompanying CTDs but without scm. The D-dimer plasma levels were significantly increased in group 3 compared with healthy subjects and those in groups 1 and 2 (p < 0.001). The D-dimer plasma level in group 2 was significantly increased compared with healthy subjects and those in group 1 (p < 0.001). Increased D-dimer plasma levels were detected in DM patients with scm without detectable VTE, malignancy, infection or accompanying CTDs. In addition to the known risk factors for increased plasma D-dimer levels in DM patients, including VTE, malignancy, infection and other accompanying autoimmune diseases, the presence of cutaneous manifestations should be considered as a new clinical risk factor.
A Human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine
Authors: Plummer Simon , Wallace Stephanie , Ball Graeme , Lloyd Roslyn , Schiapparelli Paula , Quiñones-Hinojosa Alfredo , Hartung Thomas , Pamies David 
Published: February 2019

AbstractA high throughput histology (microTMA) platform was applied for testing drugs against tumors in a novel 3D heterotypic glioblastoma brain sphere (gBS) model consisting of glioblastoma tumor cells, iPSC-derived neurons, glial cells and astrocytes grown in a spheroid. The differential responses of gBS tumors and normal neuronal cells to sustained treatments with anti-cancer drugs temozolomide (TMZ) and doxorubicin (DOX) were investigated. gBS were exposed to TMZ or DOX over a 7-day period. Untreated gBS tumors increased in size over a 4-week culture period, however, there was no increase in the number of normal neuronal cells. TMZ (100 uM) and DOX (0.3 uM) treatments caused ~30% (P~0.07) and ~80% (P < 0.001) decreases in the size of the tumors, respectively. Neither treatment altered the number of normal neuronal cells in the model. The anti-tumor effects of TMZ and DOX were mediated in part by selective induction of apoptosis. This platform provides a novel approach for screening new anti-glioblastoma agents and evaluating different treatment options for a given patient.
Impact of student-induced disturbance on stream macroinvertebrates differs among habitat types
Authors: Bossley Jon P. , Smiley Peter C. 
Published: February 2019

AbstractEnvironmental impacts from ecotourism and outdoor recreation activities on terrestrial and aquatic ecosystems are well-reported in the literature, but less is known regarding the impacts of outdoor environmental education activities. Student activity during stream classes may cause substrate disruption and localized impacts on stream macroinvertebrates. We hypothesized that student activity would negatively impact macroinvertebrate community structure in three habitat types (riffle, run, pool) within a site regularly used for stream classes while no impact from student activity would occur in the same three habitat types within an unused site. We addressed the hypothesis by sampling macroinvertebrates monthly for one year in the riffles, runs, and pools at the class site and the unused site within a fourth order stream in central Ohio. The results indicated reduced macroinvertebrate abundance and richness in the riffle at the class site during periods with student activity and no differences between site types during periods without student activity. No impacts of stream classes on macroinvertebrate communities were observed in runs or pools. The results suggest that environmental education organizations should avoid repetitive use of the same site for their stream classes to avoid reductions of macroinvertebrate abundance and taxa richness that can impact the students’ educational experience.
Performance of Cystatin C-Based Equations for Estimation of Glomerular Filtration Rate in Diabetes Patients: A Prisma-Compliant Systematic Review and Meta-Analysis
Authors: Cheuiche Amanda Veiga , Queiroz Marina , Azeredo-da-Silva André Luis Ferreira , Silveiro Sandra Pinho 
Published: February 2019

AbstractThe accuracy of estimated glomerular filtration rate (eGFR) equations in diabetes mellitus (DM) patients has been extensively questioned. We evaluated the performance of cystatin C-based equations alone or in combination with creatinine to estimate GFR in DM patients. A PRISMA-compliant systematic review was performed in the MEDLINE and Embase databases, with “diabetes mellitus” and “cystatin C” as search terms. Studies comparing cystatin C-based eGFR equations with measured GFR (mGFR) in DM patients were eligible. Accuracies P10, P15, P20, and P30 indicated the proportion of eGFR results within 10, 15, 20, and 30% of mGFR. Single-arm meta-analyses were conducted, and the Quality of Diagnostic Accuracy Studies-II tool (QUADAS-2) was applied. Twenty-three studies comprising 7065 participants were included, and 24 equations were analyzed in a broad range of GFRs. Meta-analyses were completed for 10 equations. The mean P30 accuracies of the equations ranged from 41% to 87%, with the highest values found with both CKD-EPI equations. Mean P10-P15 achieved 35% in the best scenario. A sensitivity analysis to evaluate different mGFR methods did not change results. In conclusion, cystatin C-based eGFR equations represent measured GFR fairly at best in DM patients, with high variability among the several proposed equations.
Cyclopamine tartrate, a modulator of hedgehog signaling and mitochondrial respiration, effectively arrests lung tumor growth and progression
Authors: Kalainayakan Sarada Preeta , Ghosh Poorva , Dey Sanchareeka , Fitzgerald Keely E. , Sohoni Sagar , Konduri Purna Chaitanya , Garrossian Massoud , Liu Li , Zhang Li 
Published: February 2019

AbstractLung cancer remains the leading cause of cancer-related death, despite the advent of targeted therapies and immunotherapies. Therefore, it is crucial to identify novel molecular features unique to lung tumors. Here, we show that cyclopamine tartrate (CycT) strongly suppresses the growth of subcutaneously implanted non-small cell lung cancer (NSCLC) xenografts and nearly eradicated orthotopically implanted NSCLC xenografts. CycT reduces heme synthesis and degradation in NSCLC cells and suppresses oxygen consumption in purified mitochondria. In orthotopic tumors, CycT decreases the levels of proteins and enzymes crucial for heme synthesis, uptake, and oxidative phosphorylation (OXPHOS). CycT also decreases the levels of two regulators promoting OXPHOS, MYC and MCL1, and effectively alleviates tumor hypoxia. Evidently, CycT acts via multiple modes to suppress OXPHOS. One mode is to directly inhibit mitochondrial respiration/OXPHOS. Another mode is to inhibit heme synthesis and degradation. Both modes appear to be independent of hedgehog signaling. Addition of heme to NSCLC cells partially reverses the effect of CycT on oxygen consumption, proliferation, and tumorigenic functions. Together, our results strongly suggest that CycT suppress tumor growth in the lung by inhibiting heme metabolism and OXPHOS. Targeting heme metabolism and OXPHOS may be an effective strategy to combat lung cancer.
Plastic flow anisotropy drives shear fracture
Authors: Benzerga A. Amine , Thomas Nithin , Herrington Joshua S. 
Published: February 2019

AbstractFracture of initially crack-free bodies often occurs due to plastic instabilities known as shear bands. Previous computer simulations advanced a myriad of mechanisms to rationalize shear banding. However, they were restricted to planar geometries. We investigate the relevance of anisotropic plasticity by picking an axisymmetric tensile test rig, in which shear localization is rarely observed. The three-dimensional finite-element simulations of shear banding in this type of specimens are the first of their kind. The micromechanical modeling covers a range of competing mechanisms believed to be responsible for such failure. We show that anisotropic plasticity can effectively trigger shear bands thereby causing failure of ductile solids. Our results enable shear fracture to be rationalized in ductile rocks and mitigated against in designing advanced materials.
Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus
Authors: Tahir ul Qamar Muhammad , Maryam Arooma , Muneer Iqra , Xing Feng , Ashfaq Usman Ali , Khan Faheem Ahmed , Anwar Farooq , Geesi Mohammed H. , Khalid Rana Rehan , Rauf Sadaf Abdul , Siddiqi Abdul Rauf 
Published: February 2019

AbstractEmergence of Dengue as one of the deadliest viral diseases prompts the need for development of effective therapeutic agents. Dengue virus (DV) exists in four different serotypes and infection caused by one serotype predisposes its host to another DV serotype heterotypic re-infection. We undertook virtual ligand screening (VLS) to filter compounds against DV that may inhibit inclusively all of its serotypes. Conserved non-structural DV protein targets such as NS1, NS3/NS2B and NS5, which play crucial role in viral replication, infection cycle and host interaction, were selected for screening of vital antiviral drug leads. A dataset of plant based natural antiviral derivatives was developed. Molecular docking was performed to estimate the spatial affinity of target compounds for the active sites of DV’s NS1, NS3/NS2B and NS5 proteins. The drug likeliness of the screened compounds was followed by ADMET analysis whereas the binding behaviors were further elucidated through molecular dynamics (MD) simulation experiments. VLS screened three potential compounds including Canthin-6-one 9-O-beta-glucopyranoside, Kushenol W and Kushenol K which exhibited optimal binding with all the three conserved DV proteins. This study brings forth novel scaffolds against DV serotypes to serve as lead molecules for further optimization and drug development against all DV serotypes with equal effect against multiple disease causing DV proteins. We therefore anticipate that the insights given in the current study could be regarded valuable towards exploration and development of a broad-spectrum natural anti-dengue therapy.
Prediction of Optimal Drug Schedules for Controlling Autophagy
Authors: Shirin Afroza , Klickstein Isaac S. , Feng Song , Lin Yen Ting , Hlavacek William S. , Sorrentino Francesco 
Published: February 2019

AbstractThe effects of molecularly targeted drug perturbations on cellular activities and fates are difficult to predict using intuition alone because of the complex behaviors of cellular regulatory networks. An approach to overcoming this problem is to develop mathematical models for predicting drug effects. Such an approach beckons for co-development of computational methods for extracting insights useful for guiding therapy selection and optimizing drug scheduling. Here, we present and evaluate a generalizable strategy for identifying drug dosing schedules that minimize the amount of drug needed to achieve sustained suppression or elevation of an important cellular activity/process, the recycling of cytoplasmic contents through (macro)autophagy. Therapeutic targeting of autophagy is currently being evaluated in diverse clinical trials but without the benefit of a control engineering perspective. Using a nonlinear ordinary differential equation (ODE) model that accounts for activating and inhibiting influences among protein and lipid kinases that regulate autophagy (MTORC1, ULK1, AMPK and VPS34) and methods guaranteed to find locally optimal control strategies, we find optimal drug dosing schedules (open-loop controllers) for each of six classes of drugs and drug pairs. Our approach is generalizable to designing monotherapy and multi therapy drug schedules that affect different cell signaling networks of interest.
The effect of 16S rRNA region choice on bacterial community metabarcoding results
Authors: Bukin Yu. S. , Galachyants Yu. P. , Morozov I. V. , Bukin S. V. , Zakharenko A. S. , Zemskaya T. I. 
Published: February 2019

AbstractIn this work, we compare the resolution of V2-V3 and V3-V4 16S rRNA regions for the purposes of estimating microbial community diversity using paired-end Illumina MiSeq reads, and show that the fragment, including V2 and V3 regions, has higher resolution for lower-rank taxa (genera and species). It allows for a more precise distance-based clustering of reads into species-level OTUs. Statistically convergent estimates of the diversity of major species (defined as those that together are covered by 95% of reads) can be achieved at the sample sizes of 10000 to 15000 reads. The relative error of the Shannon index estimate for this condition is lower than 4%.
The sequence and de novo assembly of Oxygymnocypris stewartii genome
Authors: Liu Hai-Ping , Xiao Shi-Jun , Wu Nan , Wang Di , Liu Yan-Chao , Zhou Chao-Wei , Liu Qi-Yong , Yang Rui-Bin , Jiang Wen-Kai , Liang Qi-Qi , Wangjiu  , Zhang Chi , Gong Jun-Hua , Yuan Xiao-Hui , Mou Zhen-Bo 
Published: February 2019

AbstractAnimal genomes in the Qinghai-Tibetan Plateau provide valuable resources for scientists to understand the molecular mechanism of environmental adaptation. Tibetan fish species play essential roles in the local ecology; however, the genomic information for native fishes was still insufficient. Oxygymnocypris stewartii, belonging to Oxygymnocypris genus, Schizothoracinae subfamily, is a native fish in the Tibetan plateau living within the elevation from roughly 3,000 m to 4,200 m. In this report, PacBio and Illumina sequencing platform were used to generate ~385.3 Gb genomic sequencing data. A genome of about 1,849.2 Mb was obtained with a contig N50 length of 257.1 kb. More than 44.5% of the genome were identified as repetitive elements, and 46,400 protein-coding genes were annotated in the genome. The assembled genome can be used as a reference for future population genetic studies of O. stewartii and will improve our understanding of high altitude adaptation of fishes in the Qinghai-Tibetan Plateau.
Fast fault detection during power swing on a hybrid transmission line using WPT
Authors: Patel Bikash , Bera Parthasarathi 
Published: February 2019

This paper presents a new technique for very high speed detection of fault during power swing on a hybrid transmission line consisting of an overhead line and an underground cable. The wavelet packet transform with the mother wavelet db1 is utilised to segregate the high‐frequency components from three‐phase current signals recorded at the relay point and a fault detection index is calculated using these components to detect faults during power swing. The proposed method is tested on a 400 kV double circuit transmission system and a 400 kV 3‐machine 9‐bus Western System Coordinating Council system simulated in electromagnetic transient program software for both symmetrical and asymmetrical faults, different fault resistances, load angles, and fault inception times at random locations on the transmission line. Its performance is also analysed for close‐in faults, high dc offset current, and the faults on the series compensated transmission line. The method is very fast to detect faults during power swing irrespective of the variations of fault conditions, and a comparative assessment with the existing methods justifies its merit.
Das Low anterior Resection Syndrome (LARS)
Authors: Sulkowski Udo , Mennigen Rudolf 
Published: February 2019

Zusammenfassung
Hintergrund Mit einem 5-Jahres-Überleben von mittlerweile 80% rückt die postoperative Lebensqualität nach onkologischer Rektumresektion zunehmend in den Fokus des Interesses. Das Low anterior Resection Syndrome (LARS) fasst die postoperative Morbidität infolge des operativen Eingriffes zusammen.
Material und Methode Es wurde eine selektive Literaturrecherche durchgeführt, um das Bild des LARS näher zu definieren und Verständnis für seine Pathophysiologie, Diagnose, Therapie und Prophylaxe zu entwickeln.
Ergebnisse LARS wird in bis zu 80% nach allen stomavermeidenden operativen Eingriffen beobachtet, die beim Rektumkarzinom durchgeführt werden. Die Kapazität des Rektumstumpfes wie auch die Verletzung nervaler Strukturen scheinen die wichtigsten pathogenetischen Faktoren zu sein, die zu einer signifikanten Einschränkung der Lebensqualität führen.
Schlussfolgerungen Es existieren verschiedene therapeutische Ansätze, um die Konsequenzen des LARS beim einzelnen Patienten abzuschwächen. Nichtsdestotrotz wird in der Zukunft noch viel Arbeit notwendig sein, um nicht nur das Überleben, sondern auch die Lebensqualität nach einem Rektumkarzinom zu verbessern.