bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hierarchy of human IgG recognition within the Staphylococcus aureus immunome
Authors: Radke Emily E. , Brown Stuart M. , Pelzek Adam J. , Fulmer Yi , Hernandez David N. , Torres Victor J. , Thomsen Isaac P. , Chiang William K. , Miller Andy O. , Shopsin Bo , Silverman Gregg J. 
Published: August 2018

AbstractStaphylococcus aureus is an opportunistic pathogen that causes a range of serious infections associated with significant morbidity, by strains increasingly resistant to antibiotics. However, to date all candidate vaccines have failed to induce protective immune responses in humans. We need a more comprehensive understanding of the antigenic targets important in the context of human infection. To investigate infection-associated immune responses, patients were sampled at initial presentation and during convalescence from three types of clinical infection; skin and soft tissue infection (SSTI), prosthetic joint infection (PJI) and pediatric hematogenous osteomyelitis (PHO). Reactivity of serum IgG was tested with an array of recombinant proteins, representing over 2,652 in-vitro-translated open reading frames (ORFs) from a community-acquired methicillin-resistant S. aureus USA300 strain. High-level reactivity was demonstrated for 104 proteins with serum IgG in all patient samples. Overall, high-level IgG-reactivity was most commonly directed against a subset of secreted proteins. Although based on limited surveys, we found subsets of S. aureus proteins with differential reactivity with serum samples from patients with different clinical syndromes. Together, our studies have revealed a hierarchy within the diverse proteins of the S. aureus “immunome”, which will help to advance efforts to develop protective immunotherapeutic agents.
Genome wide association study identifies novel potential candidate genes for bovine milk cholesterol content
Authors: Do Duy N. , Schenkel Flavio S. , Miglior Filippo , Zhao Xin , Ibeagha-Awemu Eveline M. 
Published: August 2018

AbstractThis study aimed to identify single nucleotide polymorphisms (SNPs) associated with milk cholesterol (CHL) content via a genome wide association study (GWAS). Milk CHL content was determined by gas chromatography and expressed as mg of CHL in 100 g of fat (CHL_fat) or in 100 mg of milk (CHL_milk). GWAS was performed with 1,183 cows and 40,196 SNPs using a univariate linear mixed model. Two and 20 SNPs were significantly associated with CHL_fat and CHL_milk, respectively. The important regions for CHL_fat and CHL_milk were at 41.9 Mb on chromosome (BTA) 17 and 1.6–3.2 Mb on BTA 14, respectively. DGAT1, PTPN1, INSIG1, HEXIM1, SDS, and HTR5A genes, also known to be associated with human plasma CHL phenotypes, were identified as potential candidate genes for bovine milk CHL. Additional new potential candidate genes for milk CHL were RXFP1, FAM198B, TMEM144, CXXC4, MAML2 and CDH13. Enrichment analyses suggested that identified candidate genes participated in cell-cell signaling processes and are key members in tight junction, focal adhesion, Notch signaling and glycerolipid metabolism pathways. Furthermore, identified transcription factors such as PPARD, LXR, and NOTCH1 might be important in the regulation of bovine milk CHL content. The expression of several positional candidate genes (such as DGAT1, INSIG1 and FAM198B) and their correlation with milk CHL content were further confirmed with RNA sequence data from mammary gland tissues. This is the first GWAS on bovine milk CHL. The identified markers and candidate genes need further validation in a larger cohort for use in the selection of cows with desired milk CHL content.
Metabolome and molecular basis for carbohydrate increase and nitrate reduction in burley tobacco seedlings by glycerol through upregulating carbon and nitrogen metabolism
Authors: Li Yafei , Chang Dong , Yang Huijuan , Wang Jing , Shi Hongzhi 
Published: August 2018

AbstractBurley tobacco (Nicotiana Tabacum) is a chlorophyll-deficiency mutant. Nitrate is one precursor of tobacco-specific nitrosamines (TSNAs) and is largely accumulated in burley tobacco. To decrease nitrate accumulation in burley tobacco, glycerol, a polyhydric alcohol compound and physiological regulating material, was sprayed and its effects were investigated based on metabolomic technology and molecular biology. The results showed that glucose, glutamine and glutamic acid increased by 2.6, 5.1 and 196, folds, respectively, in tobacco leaves after glycerol application. Nitrate content was significantly decreased by 12–16% and expression of eight genes responsible for carbon and nitrogen metabolism were up-regulated with glycerol applications under both normal and 20% reduced nitrogen levels (P < 0.01). Leaf biomass of plants sprayed with glycerol and 20% nitrogen reduction was equivalent to that of no glycerol control with normal nitrogen application. Carbohydrates biosynthesis, nitrate transport and nitrate assimilation were enhanced in glycerol sprayed burley tobacco seedlings which might contribute to reduced nitrate and increased carbohydrates contents. In conclusion, glyerol spray coupled with 20% nitrogen reduction would be an effective method to reduce nitrate accumulation in burley tobacco.
Characterization of Mutations in the Mitochondrial Encoded Electron Transport Chain Complexes in Acute Myeloid Leukemia
Authors: Wu Sharon , Akhtari Mojtaba , Alachkar Houda 
Published: August 2018

AbstractAcute Myeloid Leukemia is a devastating and heterogeneous, hematological malignancy characterized by the uncontrolled proliferation of undifferentiated myeloid progenitor cells—blasts. Mutations in certain mitochondrial proteins, such as IDH2 have been shown to contribute to leukemogenesis. However, the role of mutations in mitochondrial-encoded Electron Transport Chain (ETC) genes have thus far not been well elucidated in AML. Here, we use TCGA data to characterize mutations in the ETC genes and their association with clinical outcomes in AML. We found that mitochondrial ETC mutations—in Complex I, III, IV and/or V (ATP Synthase)—were present in 8% of patients with AML and were significantly more frequent in older patients. Patients with ETC mutations had worse overall survival than ETC wild type patients (OS: 9.3 vs 20.1 months; p-value: 0.007). Additionally, mutations in either or both Complex I and IV were associated with TP53 mutations (p-value: 0.009), and among TP53 mutated patients, mutations in either or both Complex I and IV were significantly associated with worse overall survival (OS: 0.85 vs 9.4 months; p-value: 0.008). Elucidation of the mechanisms by which ETC mutations contribute to AML pathogenesis and progression would facilitate the development of novel therapeutic targets.
Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders
Authors: Hall Sara , Janelidze Shorena , Surova Yulia , Widner Håkan , Zetterberg Henrik , Hansson Oskar 
Published: August 2018

AbstractInflammation has been implicated in the pathogenesis of Parkinson’s disease (PD). We here investigate levels of inflammatory biomarkers in cerebrospinal fluid (CSF) in PD and atypical parkinsonian disorders (APD) compared with neurologically healthy controls. We included 131 patients with PD and 27 PD with dementia (PDD), 24 with multiple system atrophy (MSA), 14 with progressive supranuclear palsy (PSP) and 50 controls, all part of the Swedish BioFINDER study. CSF was analyzed for CRP, SAA, IL-6, IL-8, YKL-40 and MCP-1 (CCL2) as well as α-synuclein (α-syn), tau, tau phosphorylated at Thr181 (P-tau), Aβ42 and NfL. In this exploratory study, we found higher levels of the inflammatory biomarker SAA in PDD and MSA compared with controls and PD and higher levels of CRP in PDD and MSA compared with PD. YKL-40 was lower in PD compared with controls. There were multiple positive correlations between the inflammatory markers, α-syn and markers of neuroaxonal injury (NfL and tau). In PD, higher levels of inflammatory biomarkers correlated with worse motor function and cognitive impairment. Thus, inflammatory biomarkers were increased in PDD and MSA. Furthermore, inflammatory biomarkers correlated with more severe disease regarding motor symptoms and cognitive impairment in PD, indicating an association between inflammation and more aggressive disease course. However, the results need confirmation in follow-up studies.
A systematic review and meta-analysis of prognostic biomarkers in resectable esophageal adenocarcinomas
Authors: Creemers Aafke , Ebbing Eva A. , Pelgrim Thomas C. , Lagarde Sjoerd M. , van Etten-Jamaludin Faridi S. , van Berge Henegouwen Mark I. , Hulshof Maarten C. C. M. , Krishnadath Kausilia K. , Meijer Sybren L. , Bijlsma Maarten F. , van Oijen Martijn G. H. , van Laarhoven Hanneke W. M. 
Published: August 2018

AbstractTargeted therapy is lagging behind in esophageal adenocarcinoma (EAC). To guide the development of new treatment strategies, we provide an overview of the prognostic biomarkers in resectable EAC treated with curative intent. The Medline, Cochrane and EMBASE databases were systematically searched, focusing on overall survival (OS). The quality of the studies was assessed using a scoring system ranging from 0–7 points based on modified REMARK criteria. To evaluate all identified prognostic biomarkers, the hallmarks of cancer were adapted to fit all biomarkers based on their biological function in EAC, resulting in the features angiogenesis, cell adhesion and extra-cellular matrix remodeling, cell cycle, immune, invasion and metastasis, proliferation, and self-renewal. Pooled hazard ratios (HR) and 95% confidence intervals (CI) were derived by random effects meta-analyses performed on each hallmarks of cancer feature. Of the 3298 unique articles identified, 84 were included, with a mean quality of 5.9 points (range 3.5–7). The hallmarks of cancer feature ‘immune’ was most significantly associated with worse OS (HR 1.88, (95%CI 1.20–2.93)). Of the 82 unique prognostic biomarkers identified, meta-analyses showed prominent biomarkers, including COX-2, PAK-1, p14ARF, PD-L1, MET, LC3B, IGFBP7 and LGR5, associated to each hallmark of cancer.
Quantitative Proteomic Analysis of 2D and 3D Cultured Colorectal Cancer Cells: Profiling of Tankyrase Inhibitor XAV939-Induced Proteome
Authors: Kim Young Eun , Jeon Hyo Jin , Kim Dahee , Lee Sun Young , Kim Ki Young , Hong Jongki , Maeng Pil Jae , Kim Kwang-Rok , Kang Dukjin 
Published: August 2018

AbstractRecently there has been a growing interest in three-dimensional (3D) cell culture systems for drug discovery and development. These 3D culture systems better represent the in vivo cellular environment compared to two-dimensional (2D) cell culture, thereby providing more physiologically reliable information on drug screening and testing. Here we present the quantitative profiling of a drug-induced proteome in 2D- and 3D-cultured colorectal cancer SW480 cells using 2D nanoflow liquid chromatography-tandem mass spectrometry (2D-nLC-MS/MS) integrated with isobaric tags for relative and absolute quantitation (iTRAQ). We identified a total of 4854 shared proteins between 2D- and 3D-cultured SW480 cells and 136/247 differentially expressed proteins (up/down-regulated in 3D compared to 2D). These up/down-regulated proteins were mainly involved in energy metabolism, cell growth, and cell-cell interactions. We also investigated the XAV939 (tankyrase inhibitor)-induced proteome to reveal factors involved in the 3D culture-selective growth inhibitory effect of XAV939 on SW480 cells. We identified novel XAV939-induced proteins, including gelsolin (a possible tumor suppressor) and lactate dehydrogenase A (a key enzyme of glycolysis), which were differentially expressed between 2D- and 3D-cultured SW480 cells. These results provide a promising informative protein dataset to determine the effect of XAV939 on the expression levels of proteins involved in SW480 cell growth.
MARCKS regulates neuritogenesis and interacts with a CDC42 signaling network
Authors: Brudvig J. J. , Cain J. T. , Sears R. M. , Schmidt-Grimminger G. G. , Wittchen E. S. , Adler K. B. , Ghashghaei H. T. , Weimer J. M. 
Published: August 2018

AbstractThrough the process of neuronal differentiation, newly born neurons change from simple, spherical cells to complex, sprawling cells with many highly branched processes. One of the first stages in this process is neurite initiation, wherein cytoskeletal modifications facilitate membrane protrusion and extension from the cell body. Hundreds of actin modulators and microtubule-binding proteins are known to be involved in this process, but relatively little is known about how upstream regulators bring these complex networks together at discrete locations to produce neurites. Here, we show that Myristoylated alanine-rich C kinase substrate (MARCKS) participates in this process. Marcks−/− cortical neurons extend fewer neurites and have less complex neurite arborization patterns. We use an in vitro proteomics screen to identify MARCKS interactors in developing neurites and characterize an interaction between MARCKS and a CDC42-centered network. While the presence of MARCKS does not affect whole brain levels of activated or total CDC42, we propose that MARCKS is uniquely positioned to regulate CDC42 localization and interactions within specialized cellular compartments, such as nascent neurites.
A comparison of trunk circumference and width indices for hypertension and type 2 diabetes in a large-scale screening: a retrospective cross-sectional study
Authors: Lee Bum Ju , Ku Boncho 
Published: August 2018

AbstractAnthropometric indices determine important risk factors for many chronic diseases. However, to date, no study has simultaneously analyzed the capabilities of trunk circumference and width indices to identify hypertension and type 2 diabetes in a large-scale screening study. The objectives of this study were to examine the associations of hypertension and - diabetes with circumference and width indices measured at the five identical positions (axillary, chest, rib, waist, and pelvic) and to compare the capabilities of circumference and width indices to identify the two diseases. Data were obtained from the Korean Health and Genome Epidemiology Study database. The associations and abilities of the circumference indices to identify diabetes were greater than those for hypertension. Overall, trunk circumference indices displayed stronger associations with and greater abilities to identify hypertension and diabetes than did trunk width indices at the five positions. In the comparative analysis between index pairs of circumference and width in patients with diabetes, significant differences were shown at all five positions and in the adjusted analysis of axillary, chest, rib, and pelvic positions. Therefore, width indices should not be used as an alternative indicator of type 2 diabetes in either men or women, except when measured at the waist.
Stretchable and Washable Strain Sensor Based on Cracking Structure for Human Motion Monitoring
Authors: Tolvanen Jarkko , Hannu Jari , Jantunen Heli 
Published: August 2018

AbstractStretchable and wearable strain sensors have been intensively studied in recent years for applications in human motion monitoring. However, achieving a high-performance strain sensor with high stretchability, ultra-sensitivity, and functionality, such as tunable sensing ranges and sensitivity to various stimuli, has not yet been reported, even though such sensors have great importance for the future applications of wearable electronics. Herein, a novel and versatile strain sensor based on a cracking (silver ink patterned silicone elastomer)-(silver plated nylon structure) (Ag-DS/CF) has been designed and fabricated. The unique structure combined precisely shaped stretchable conductive fabrics and wrinkled Ag-ink pattern to achieve an excellent electrical performance. The Ag-DS/CF could be used to detect both large and subtle human motions and activities, pressure changes, and physical vibrations by achieving high stretchability up to 75%, ultrahigh sensitivity (gauge factor >104–106), tunable sensing ranges (from 7 to 75%). Excellent durability was demonstrated for human motion monitoring with machine washability. The extremely versatile Ag-DS/CF showed outstanding potential for the future of wearable electronics in real-time monitoring of human health, sports performance, etc.
The DNMT3A R882H mutation does not cause dominant negative effects in purified mixed DNMT3A/R882H complexes
Authors: Emperle Max , Dukatz Michael , Kunert Stefan , Holzer Katharina , Rajavelu Arumugam , Jurkowska Renata Z. , Jeltsch Albert 
Published: August 2018

AbstractThe DNA methyltransferase DNMT3A R882H mutation is observed in 25% of all AML patients. DNMT3A is active as tetramer and the R882H mutation is located in one of the subunit/subunit interfaces. Previous work has reported that formation of mixed wildtype/R882H complexes leads to a strong loss of catalytic activity observed in in vitro DNA methylation assays (Russler-Germain et al., 2014, Cancer Cell 25:442–454). To investigate this effect further, we have prepared mixed wildtype/R882H DNMT3A complexes by incubation of individually purified subunits of the DNMT3A catalytic domain and full-length DNMT3A2. In addition, we have used a double affinity tag approach and specifically purified mixed catalytic domain complexes formed after co-expression of R882H and wildtype subunits in E. coli cells. Afterwards, we determined the catalytic activity of the mixed complexes and compared it to that of purified complexes only consisting of one subunit type. In both settings, the expected catalytic activities of mixed R882H/wildtype complexes were observed demonstrating an absence of a dominant negative effect of the R882H mutation in purified DNMT3A enzymes. This result suggests that heterocomplex formation of DNMT3A and R882H is unlikely to cause dominant negative effects in human cells as well. The limitations of this conclusion and its implications are discussed.
Strongly Coupled Morphological Features of Aortic Aneurysms Drive Intraluminal Thrombus
Authors: Bhagavan D. , Di Achille P. , Humphrey J. D. 
Published: August 2018

AbstractOver 75% of abdominal aortic aneurysms harbor an intraluminal thrombus, and increasing evidence suggests that biologically active thrombus contributes to the natural history of these potentially lethal lesions. Thrombus formation depends on the local hemodynamics, which in turn depends on morphological features of the aneurysm and near vasculature. We previously presented a hemodynamically motivated “thrombus formation potential” that predicts where and when thrombus might form. Herein, we combine detailed studies of the three-dimensional hemodynamics with methods of sparse grid collocation and interpolation via kriging to examine roles of five key morphological features of aneurysms on thrombus formation: lesion diameter, axial position, length, curvature, and renal artery position. Computational simulations suggest that maximum diameter is a key determinant of thrombogenicity, but other morphological features modulate this dependence. More distally located lesions tend to have a higher thrombus formation potential and shorter lesions tend to have a higher potential than longer lesions, given the same aneurysmal dilatation. Finally, movement of vortical structures through the infrarenal aorta and lesion can significantly affect thrombogenicity. Formation of intraluminal thrombus within an evolving abdominal aortic aneurysm thus depends on coupled morphological features, not all intuitive, and computational simulations can be useful for predicting thrombogenesis.
Velocity distributions in trapped and mobilized non-wetting phase ganglia in porous media
Authors: Zarikos I. , Terzis A. , Hassanizadeh S. M. , Weigand B. 
Published: August 2018

AbstractUnderstanding the mobilisation of trapped globules of non-wetting phase during two-phase flow has been the aim of numerous studies. However, the driving forces for the mobilisation of the trapped phases are still not well understood. Also, there is little information about what happens within a globule before, at the onset and during mobilization. In this work, we used micro-particle tracking velocimetry in a micro-fluidic model in order to visualise the velocity distributions inside the trapped phase globules prior and during mobilisation. Therefore, time-averaged and instantaneous velocity vectors have been determined using fluorescent microscopy. As a porous medium, we used a polydimethylsiloxane (PDMS) micro-model with a well-defined pore structure, where drainage and imbibition experiments were conducted. Three different geometries of trapped non-wetting globules, namely droplets, blobs and ganglia were investigated. We observed internal circulations inside the trapped phase globules, leading to the formation of vortices. The direction of circulating flow within a globule is dictated by the drag force exerted on it by the flowing wetting phase. This is illustrated by calculating and analyzing the drag force (per unit area) along fluid-fluid interfaces. In the case of droplets and blobs, only one vortex is formed. The flow field within a ganglion is much more complex and more vortices can be formed. The circulation velocities are largest at the fluid-fluid interfaces, along which the wetting phase flows and decreases towards the middle of the globule. The circulation velocities increased proportionally with the increase of wetting phase average velocity (or capillary number). The vortices remain stable as long as the globules are trapped, start to change at the onset of mobilization and disappear during the movement of globules. They reappear when the globules get stranded. Droplets are less prone to mobilization; blobs get mobilised in whole; while ganglia may get ruptured and get mobilised only partially.
Machine learning identified an Alzheimer’s disease-related FDG-PET pattern which is also expressed in Lewy body dementia and Parkinson’s disease dementia
Authors: Katako Audrey , Shelton Paul , Goertzen Andrew L. , Levin Daniel , Bybel Bohdan , Aljuaid Maram , Yoon Hyun Jin , Kang Do Young , Kim Seok Min , Lee Chong Sik , Ko Ji Hyun 
Published: August 2018

AbstractUtilizing the publicly available neuroimaging database enabled by Alzheimer’s disease Neuroimaging Initiative (ADNI; http://adni.loni.usc.edu/), we have compared the performance of automated classification algorithms that differentiate AD vs. normal subjects using Positron Emission Tomography (PET) with fluorodeoxyglucose (FDG). General linear model, scaled subprofile modeling and support vector machines were examined. Among the tested classification methods, support vector machine with Iterative Single Data Algorithm produced the best performance, i.e., sensitivity (0.84) × specificity (0.95), by 10-fold cross-validation. We have applied the same classification algorithm to four different datasets from ADNI, Health Science Centre (Winnipeg, Canada), Dong-A University Hospital (Busan, S. Korea) and Asan Medical Centre (Seoul, S. Korea). Our data analyses confirmed that the support vector machine with Iterative Single Data Algorithm showed the best performance in prediction of future development of AD from the prodromal stage (mild cognitive impairment), and that it was also sensitive to other types of dementia such as Parkinson’s Disease Dementia and Dementia with Lewy Bodies, and that perfusion imaging using single photon emission computed tomography may achieve a similar accuracy to that of FDG-PET.