bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of the Student Engagement Behaviour at the Faculty Level in a University
Authors: Lan Nguyen Thu
Published: December 2019

The application of service-dominant logic (SDL) is the background for analyzing student engagement behaviour in this research. The case setting is the Faculty of Marketing belonging to National Economics University (NEU), Hanoi, Vietnam. The purpose is to investigate the types and the role of student engagement behaviour. Also, this study will identify antecedents affecting student engagement behaviour. This study used the case study method and data were collected through in-depth and focus group interviewing. A total of 25 undergraduate students at the Faculty of Marketing, NEU, Hanoi, were interviewed for this study. Findings show that among four types of student engagement behaviours, augmenting and influencing behaviour are the two most popular. The main findings indicated antecedents affecting customer engagement behaviours (CEBs) belonging to student-based and university-based factors. The most important antecedents in student-based factors are identified as the sense of initiative and student perception about the marketing occupation. The influential antecedents in university-based factors include the service provider’s career and vocational orientation, platforms for information exchange and feedback to student engagement behaviour. Based on the results, some managerial implications for the university and the faculty are proposed. Further, the research offers three research propositions related to the most important antecedents: the sense of initiative, the service provider’s career and vocational orientation and the reflective platform for information exchange and feedback towards CEB, which will have a positive effect on student engagement behaviour.
Do Informal Forums Matter? Lessons from Nepal’s Local Policymaking
Authors: Bhusal Thaneshwar
Published: December 2019

This research empirically explores whether and how informal forums facilitate the participation of ordinary people in the local policymaking process. Using qualitative data generated from 2014 to 2016 in the Butwal Sub-Metropolitan City in western Nepal, it argues that informal forums are the most conducive participatory platforms for ordinary people and that these forums can bring positive influences on the formal processes of policymaking. Examined through the analytical framework of society-driven participatory institutions, findings of this research suggest that informal forums, if designed properly, can contribute to securing democratic rights of ordinary people by allowing them to participate to raise and deliberate their issues in the local policymaking process. In addition to broadening the existing knowledge about the role of informal forums in local governance, findings of this research offer new insights for local authorities who are passionate about participatory local policymaking.
Atovaquone is active against AML by upregulating the integrated stress pathway and suppressing oxidative phosphorylation
Authors: Stevens Alexandra M. , Xiang Michael , Heppler Lisa N. , Tošić Isidora , Jiang Kevin , Munoz Jaime O. , Gaikwad Amos S. , Horton Terzah M. , Long Xin , Narayanan Padmini , Seashore Elizabeth L. , Terrell Maci C. , Rashid Raushan , Krueger Michael J. , Mangubat-Medina Alicia E. , Ball Zachary T. , Sumazin Pavel , Walker Sarah R. , Hamada Yoshimasa , Oyadomari Seiichi , Redell Michele S. , Frank David A.
Published: December 2019

Key Points

Atovaquone induces AML blast apoptosis and prolongs survival in AML xenografts. Atovaquone induces proapoptotic signaling and inhibits the mTOR pathway through upregulation of ATF4 and also suppresses OXPHOS.
Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting
Authors: Slomp Anne , Moesbergen Laura M. , Gong Jia-nan , Cuenca Marta , von dem Borne Peter A. , Sonneveld Pieter , Huang David C. S. , Minnema Monique C. , Peperzak Victor
Published: December 2019

Key Points

Amplification of 1q21 correlates with increased sensitivity to MCL-1 inhibitor S63845 in primary MM cells. Poor-prognosis MM is particularly sensitive to MCL-1 inhibition, partially independent of 1q21 amplification status.
RETRACTED ARTICLE: A Comparative Study of the Toxicity of Polyethylene Glycol–Coated Cobalt Ferrite Nanospheres and Nanoparticles
Authors: Akhtar Shahnaz , Khan Qasim , Anwar Shahzad , Ali Ghafar , Maqbool Muhammad , Khan Maaz , Karim Shafqat , Gao Lan
Published: December 2019

We present a comparative study of the toxicity of polyethylene glycol (PEG)–coated cobalt ferrite nanoparticles and nanospheres. Nanoparticles were prepared by hydrothermal method while nanospheres were prepared by solvothermal technique. The surface of nanomaterials was successfully modified with polyethylene glycol. To investigate the morphology of the prepared samples, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, thermogravimetric analysis (TGA), and electron microscopy techniques were employed. Structural analyses confirmed the formation of polycrystalline cobalt ferrite nanoparticles with diameters in the range 20–25 nm and nanospheres in the range 80–100 nm, respectively. Kunming SPF mice (female, 6–8 weeks old) were used to investigate the toxicity induced by cobalt ferrite nanoparticles and nanospheres in different organs of the mice. Biodistribution studies, biochemical indices, histopathological assessments, inflammatory factors, oxidation and antioxidant levels, and cytotoxicity tests were performed to assess the toxicity induced by cobalt ferrite nanoparticles and nanospheres in mice. Cobalt ferrite nanospheres were found to be more toxic than the nanoparticles and curcumin was proved to be a good healing agent for the toxicity induced by PEG-coated cobalt ferrite nanomaterials in mice.
Can the morality of a group whose members are interdependent be extended to all humanity and beyond?
Authors: Leigh Egbert Giles
Published: December 2019

I review David Sloan Wilson’sThis View of Life, which considers why a group’s members, if tightly interdependent, must treat each other sympathetically, justly and generously, and what actions could cause these sentiments to extend to all humanity.
The peptide transporter 1a of the zebrafish Danio rerio, an emerging model in nutrigenomics and nutrition research: molecular characterization, functional properties, and expression analysis
Authors: Vacca Francesca , Barca Amilcare , Gomes Ana S. , Mazzei Aurora , Piccinni Barbara , Cinquetti Raffaella , Del Vecchio Gianmarco , Romano Alessandro , Rønnestad Ivar , Bossi Elena , Verri Tiziano
Published: December 2019

Background

Peptide transporter 1 (PepT1, alias Slc15a1) mediates the uptake of dietary di/tripeptides in all vertebrates. However, in teleost fish, more than one PepT1-type transporter might function, due to specific whole genome duplication event(s) that occurred during their evolution leading to a more complex paralogue gene repertoire than in higher vertebrates (tetrapods).

Results

Here, we describe a novel di/tripeptide transporter in the zebrafish (Danio rerio), i.e., the zebrafish peptide transporter 1a (PepT1a; also known as Solute carrier family 15 member a1, Slc15a1a), which is a paralogue (78% similarity, 62% identity at the amino acid level) of the previously described zebrafish peptide transporter 1b (PepT1b, alias PepT1; also known as Solute carrier family 15 member 1b, Slc15a1b). Also, we report a basic analysis of the pept1a (slc15a1a) mRNA expression levels in zebrafish adult tissues/organs and embryonic/early larval developmental stages. As assessed by expression in Xenopus laevis oocytes and two-electrode voltage clamp measurements, zebrafish PepT1a, as PepT1b, is electrogenic, Na+-independent, and pH-dependent and functions as a low-affinity system, with K0.5 values for Gly-Gln at − 60 mV of 6.92 mmol/L at pH 7.6 and 0.24 mmol/L at pH 6.5 and at − 120 mV of 3.61 mmol/L at pH 7.6 and 0.45 mmol/L at pH 6.5. Zebrafish pept1a mRNA is highly expressed in the intestine and ovary of the adult fish, while its expression in early development undergoes a complex trend over time, with pept1a mRNA being detected 1 and 2 days post-fertilization (dpf), possibly due to its occurrence in the RNA maternal pool, decreasing at 3 dpf (~ 0.5-fold) and increasing above the 1–2 dpf levels at 4 to 7 dpf, with a peak (~ 7-fold) at 6 dpf.

Conclusions

We show that the zebrafish PepT1a-type transporter is functional and co-expressed with pept1b (slc15a1b) in the adult fish intestine. Its expression is also confirmed during the early phases of development when the yolk syncytial layer is present and yolk protein resorption processes are active. While completing the missing information on PepT1-type transporters function in the zebrafish, these results open to future investigations on the similar/differential role(s) of PepT1a/PepT1b in zebrafish and teleost fish physiology.
Data-driven multiscale modeling reveals the role of metabolic coupling for the spatio-temporal growth dynamics of yeast colonies
Authors: Intosalmi Jukka , Scott Adrian C. , Hays Michelle , Flann Nicholas , Yli-Harja Olli , Lähdesmäki Harri , Dudley Aimée M. , Skupin Alexander
Published: December 2019

Background

Multicellular entities like mammalian tissues or microbial biofilms typically exhibit complex spatial arrangements that are adapted to their specific functions or environments. These structures result from intercellular signaling as well as from the interaction with the environment that allow cells of the same genotype to differentiate into well-organized communities of diversified cells. Despite its importance, our understanding how this cell–cell and metabolic coupling lead to functionally optimized structures is still limited.

Results

Here, we present a data-driven spatial framework to computationally investigate the development of yeast colonies as such a multicellular structure in dependence on metabolic capacity. For this purpose, we first developed and parameterized a dynamic cell state and growth model for yeast based on on experimental data from homogeneous liquid media conditions. The inferred model is subsequently used in a spatially coarse-grained model for colony development to investigate the effect of metabolic coupling by calibrating spatial parameters from experimental time-course data of colony growth using state-of-the-art statistical techniques for model uncertainty and parameter estimations. The model is finally validated by independent experimental data of an alternative yeast strain with distinct metabolic characteristics and illustrates the impact of metabolic coupling for structure formation.

Conclusions

We introduce a novel model for yeast colony formation, present a statistical methodology for model calibration in a data-driven manner, and demonstrate how the established model can be used to generate predictions across scales by validation against independent measurements of genetically distinct yeast strains.
Automated segmentation of cardiomyocyte Z-disks from high-throughput scanning electron microscopy data
Authors: Khadangi Afshin , Hanssen Eric , Rajagopal Vijay
Published: December 2019

Background

With the advent of new high-throughput electron microscopy techniques such as serial block-face scanning electron microscopy (SBF-SEM) and focused ion-beam scanning electron microscopy (FIB-SEM) biomedical scientists can study sub-cellular structural mechanisms of heart disease at high resolution and high volume. Among several key components that determine healthy contractile function in cardiomyocytes are Z-disks or Z-lines, which are located at the lateral borders of the sarcomere, the fundamental unit of striated muscle. Z-disks play the important role of anchoring contractile proteins within the cell that make the heartbeat. Changes to their organization can affect the force with which the cardiomyocyte contracts and may also affect signaling pathways that regulate cardiomyocyte health and function. Compared to other components in the cell, such as mitochondria, Z-disks appear as very thin linear structures in microscopy data with limited difference in contrast to the remaining components of the cell.

Methods

In this paper, we propose to generate a 3D model of Z-disks within single adult cardiac cells from an automated segmentation of a large serial-block-face scanning electron microscopy (SBF-SEM) dataset. The proposed fully automated segmentation scheme is comprised of three main modules including “pre-processing”, “segmentation” and “refinement”. We represent a simple, yet effective model to perform segmentation and refinement steps. Contrast stretching, and Gaussian kernels are used to pre-process the dataset, and well-known “Sobel operators” are used in the segmentation module.

Results

We have validated our model by comparing segmentation results with ground-truth annotated Z-disks in terms of pixel-wise accuracy. The results show that our model correctly detects Z-disks with 90.56% accuracy. We also compare and contrast the accuracy of the proposed algorithm in segmenting a FIB-SEM dataset against the accuracy of segmentations from a machine learning program called Ilastik and discuss the advantages and disadvantages that these two approaches have.

Conclusions

Our validation results demonstrate the robustness and reliability of our algorithm and model both in terms of validation metrics and in terms of a comparison with a 3D visualisation of Z-disks obtained using immunofluorescence based confocal imaging.
Expression alteration of microRNAs in Nucleus Accumbens is associated with chronic stress and antidepressant treatment in rats
Authors: Song Weichen , Shen Yifeng , Zhang Yanhua , Peng Sufang , Zhang Ran , Ning Ailing , Li Huafang , Li Xia , Lin Guan Ning , Yu Shunying
Published: December 2019

Background

Nucleus Accumbens (NAc) is a vital brain region for the process of reward and stress, whereas microRNA plays a crucial role in depression pathology. However, the abnormality of NAc miRNA expression during the stress-induced depression and antidepressant treatment, as well as its biological significance, are still unknown.

Methods

We performed the small RNA-sequencing in NAc of rats from three groups: control, chronic unpredictable mild stress (CUMS), and CUMS with an antidepressant, Escitalopram. We applied an integrative pipeline for analyzing the miRNA expression alternation in different model groups, including differential expression analysis, co-expression analysis, as well as a subsequent pathway/network analysis to discover both miRNA alteration pattern and its biological significance.

Result

A total of 423 miRNAs were included in analysis.18/8 differential expressing (DE) miRNA (adjusted p < 0.05, |log2FC| > 1) were observed in controls Vs. depression/depression Vs. treatment, 2 of which are overlapping. 78% (14/18) of these miRNAs showed opposite trends of alteration in stress and treatment. Two micro RNA, miR-10b-5p and miR-214-3p, appeared to be hubs in the regulation networks and also among the top findings in both differential analyses. Using co-expression analysis, we found a functional module that strongly correlated with stress (R = 0.96, P = 0.003), and another functional module with a moderate correlation with anhedonia (R = 0.89, P = 0.02). We also found that predicted targets of these miRNAs were significantly enriched in the Ras signaling pathway, which is associated with both depression, anhedonia, and antidepressant treatment.

Conclusion

Escitalopram treatment can significantly reverse NAc miRNA abnormality induced by chronic stress. However, the novel miRNA alteration that is absent in stress pathology also emerges, which means that antidepressant treatment is unlikely to bring miRNA expression back to the same level as the controls. Also, the Ras-signaling pathway may be involved in explaining the depression disease etiology, the clinical symptom, and treatment response of stress-induced depression.
Genome-wide association study in Chinese cohort identifies one novel hypospadias risk associated locus at 12q13.13
Authors: Chen Zhongzhong , Lin Xiaoling , Lei Yunping , Chen Haitao , Finnell Richard H. , Wang Yaping , Xu Jianfeng , Lu Daru , Xie Hua , Chen Fang
Published: December 2019

Background

Hypospadias risk–associated gene variants have been reported in populations of European descent using genome-wide association studies (GWASs). There is little known at present about any possible hypospadias risk associations in Han Chinese populations.

Methods

To systematically investigate hypospadias risk–associated gene variants in Chinese patients, we performed the first GWAS in a Han Chinese cohort consisting of 197 moderate-severe hypospadias cases and 933 unaffected controls. Suggestive loci (p < 1 × 10− 4) were replicated in 118 cases and 383 controls, as well as in a second independent validation population of 137 cases and 190 controls. Regulatory and protein-protein interactions (PPIs) were then conducted for the functional analyses of candidate variants.

Results

We identified rs11170516 with the risk allele G within the SP1/SP7 region that was independently associated with moderate-severe hypospadias [SP1/SP7, rs11170516, Pcombine = 3.5 × 10− 9, odds ratio (OR) = 1.96 (1.59–2.44)]. Results also suggested that rs11170516 is associated with the expression of SP1 as a cis-expression quantitative trait locus (cis-eQTL). Protein SP1 could affect the risk of hypospadias via PPIs.

Conclusions

We performed the first GWAS of moderate-severe hypospadias in a Han Chinese cohort, and identified one novel susceptibility cis-acting regulatory locus at 12q13.13, which may regulate a variety of hypospadias-related pathways by affecting proximal SP1 gene expression and subsequent PPIs. This study complements known common hypospadias risk-associated variants and provides the possible role of cis-acting regulatory variant in causing hypospadias.
Combination of the gamma-glutamyltransferase-to-prealbumin ratio and other indicators may be a novel marker for predicting the prognosis of patients with hepatocellular carcinoma undergoing locoregional ablative therapies
Authors: Wang Q. , Zhao P. , He N. , Sun J. P. , Li K. , Zang C. R. , Zhao Y. N. , Zhao Y. , Zhang Y. H.
Published: December 2019

Objective

The aim of this study was to investigate the prognostic significance of the serum γ-glutamyltransferase (γ-GT)-to-prealbumin ratio (GPR) and whether combining this ratio with other parameters can lead to an improved prognostic value for patients with hepatocellular carcinoma (HCC) undergoing transcatheter arterial chemoembolization (TACE) combined with local ablation therapy.

Methods

A total of 235 HCC patients who were treated with combined therapies were retrospectively analyzed. The demographic data and clinicopathological data were collected. A fibrinogen (Fib)-GPR score of 2 was assigned to patients with elevated Fib and GPR values, and a score of 1 or 0 was assigned to patients with one or neither of these two markers, respectively. In addition, an N-score of 2 was assigned to patients with low neutrophil and high GPR values, and a score of 1 or 0 was assigned to patients with one or neither of these two markers, respectively. The optimal cutoff values and prognostic roles of GPR and other markers were identified according to the time-dependent receiver operating characteristic (ROC) curves and Youden’s index.

Results

Multiple tumors, high levels of α-fetoprotein (AFP) and Fib, as well as a high GPR, were found to be independent risk factors in recurrent patients, while multiple tumors, a low neutrophil count, and a high GPR were associated with reduced overall survival (OS) in patients with HCC who received combined therapies. Patients with a Fib-GPR score of 2 and N-GPR score of 2 had poor recurrence-free survival (RFS) and OS, respectively.

Conclusions

Fib-GPR and N-GPR scores may be helpful in predicting both recurrence and the prognosis of HCC patients, thereby assisting in the process to make a true clinical decision and optimize therapeutic options.
Influence of dyskalemia at admission and early dyskalemia correction on survival and cardiac events of critically ill patients
Authors:   on behalf of the OUTCOMEREA STUDY GROUP, Bouadma Lila , Mankikian Stefan , Darmon Michael , Argaud Laurent , Vinclair Camille , Siami Shidasp , Garrouste-Orgeas Maité , Papazian Laurent , Cohen Yves , Marcotte Guillaume , Styfalova Lenka , Reignier Jean , Lautrette Alexandre , Schwebel Carole , Timsit Jean-Francois
Published: December 2019

Objectives

Our objectives were (1) to characterize the distribution of serum potassium levels at ICU admission, (2) to examine the relationship between dyskalemia at ICU admission and occurrence of cardiac events, and (3) to study both the association between dyskalemia at ICU admission and dyskalemia correction by day 2 on 28-day mortality.

Design

Inception cohort study from the longitudinal prospective French multicenter OUTCOMEREA database (1999–2014)

Setting

22 French OUTCOMEREA network ICUs

Patients

Patients were classified into six groups according to their serum potassium level at admission: three groups of hypokalemia and three groups of hyperkalemia defined as serious hypokalemia [K+] < 2.5 and serious hyperkalemia [K+] > 7 mmol/L, moderate hypokalemia 2.5 ≤ [K+] < 3 mmol/L and moderate hyperkalemia 6 < [K+] ≤ 7 mmol/L, and mild hypokalemia 3 ≤ [K+] < 3.5 mmol/L and mild hyperkalemia 5 < [K+] ≤ 6 mmol/L. We sorted evolution at day 2 of dyskalemia into three categories: balanced, not-balanced, and overbalanced.

Intervention

None

Measurements and main results

Of 12,090 patients, 2108 (17.4%) had hypokalemia and 1445 (12%) had hyperkalemia.

Prognostic impact of dyskalemia and its correction was assessed using multivariate Cox models. After adjustment, hypokalemia and hyperkalemia were independently associated with a greater risk of 28-day mortality. Mild hyperkalemic patients had the highest mortality (hazard ratio (HR) 1.29, 95% confidence interval (CI) [1.13–1.47], p < 0.001). Adjusted 28-day mortality was higher if serum potassium level was not-balanced at day 2 (aHR = 1.51, 95% CI [1.30–1.76], p < 0.0001) and numerically higher but not significantly different if serum potassium level was overbalanced at day 2 (aHR = 1.157, 95% CI [0.84–1.60], p = 0.38). Occurrence of cardiac events was evaluated by logistic regression. Except for patients with serious hypokalemia at admission, the depth of dyskalemia was associated with increased risk of cardiac events.

Conclusions

Dyskalemia is common at ICU admission and associated with increased mortality. Occurrence of cardiac events increased with dyskalemia depth. A correction of serum potassium level by day 2 was associated with improved prognosis.
Efficacy of Behavioral Experiments in Cognitive Therapy for Social Anxiety Disorder: Study protocol for a randomized controlled trial
Authors: Clément Celina , Lin Jihong , Stangier Ulrich
Published: December 2019

Background

While the efficacy of cognitive therapy (CT) has been well established for social anxiety disorder (SAD) in several randomized controlled trials, there are still large differences between trials with respect to effect sizes. The present study investigates the question of whether enhanced training and the use of behavioral experiments (BEs) increases the efficacy of traditional CT, based on verbal methods of cognitive restructuring.

Methods/design

A mixed within/between conditions design will be applied, with therapists and patients being randomly allocated to one of two conditions: (1) training of CT plus BEs, (2) training of CT “as usual”.

Sixty patients with the primary diagnosis of SAD will be recruited and treated in the outpatient clinic of the Department of Psychology, University of Frankfurt. To ensure adherence to therapist protocols, all therapists will be trained and supervised by the project coordinators. In addition, videotaped treatment sessions will be independently evaluated to guarantee both adherence to protocols and the quality of the intervention. Treatment effects will be assessed by independent SAD symptom ratings using the Liebowitz Social Anxiety Scale as the primary outcome measure and self-report measures as secondary outcome measures.

Discussion

The present cognitive behavioral therapy (CBT) trial will be the first to clarify the contribution of BEs to the efficacy of CT in a randomized controlled design. Study results are relevant to clinical training and implementation of evidence-based treatments.

Trial registration

German Clinical Trials Register International Clinical Trials Registry Platform (ICTRP) identifier: DRKS00014349. Trial status: recruiting.
Regorafenib plus FOLFIRI with irinotecan dose escalated according to uridine diphosphate glucuronosyltransferase 1A1genotyping in previous treated metastatic colorectal cancer patients:study protocol for a randomized controlled trial
Authors: Ma Cheng-Jen , Chang Tsung-Kun , Tsai Hsiang-Lin , Su Wei-Chih , Huang Ching-Wen , Yeh Yung-Sung , Chang Yu-Tang , Wang Jaw-Yuan
Published: December 2019

Background

Regorafenib is an oral multikinase inhibitor for metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidines, irinotecan, oxaliplatin, monoclonal antibodies targeting vascular endothelial growth factor, and monoclonal antibodies targeting epidermal growth factor receptor. A dose reduction from 160 mg to 120 mg regorafenib reduces regorafenib-associated adverse events (AEs). Dose adjustment of irinotecan in a 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) regimen on the basis of an individual uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) genotype provides optimal oncological outcomes with acceptable AEs. The aim of this study is to address the efficacy and safety of a dose-adjusted combination of regorafenib and FOLFIRI for patients with mCRC.

Methods

A prospective, multicenter, randomized in a 2:1 ratio, controlled, clinical trial with two parallel arms will be conducted to compare irinotecan dose-escalated FOLFIRI according to UGT1A1 genotyping plus 120 mg regorafenib with 120 mg regorafenib alone in previously treated patients with mCRC. The primary endpoint is progression-free survival, and the secondary endpoints are overall survival, disease control rate, time to progression, and duration of treatment. Safety assessments will also be recorded.

Discussion

Dose adjustment for regorafenib and irinotecan makes treatment-related AEs tolerable and makes the concomitant treatment practicable. This study will provide initial evidence regarding the efficacy and safety of a new combination of chemotherapy and a targeted agent for mCRC.

Trial registration

ClinicalTrials.gov, NCT03880877. Prospectively registered on 19 March 2019.
Assessment of differences between DNA content of cell-cultured and freely suspended oocysts of Cryptosporidium parvum and their suitability as DNA standards in qPCR
Authors: Woolsey Ian D. , Blomstrand Berit , Øines Øivind , Enemark Heidi L.
Published: December 2019

Background

Although more modern methods are available, quantitative PCR (qPCR) is reproducible, sensitive and specific with instruments and expertise readily available in many laboratories. As such, the use of qPCR in Cryptosporidium research is well established and still widely used by researchers globally. This method depends upon the generation of standards at different concentrations to generate standard curves subsequently used for the quantification of DNA.

Methods

We assessed four types of DNA template used to generate standard curves in drug screening studies involving Cryptosporidium spp.: (i) serially diluted Cryptosporidium parvum oocysts (106–1); (ii) diluted template DNA from pure oocysts (×10–×106 dilution of 106 oocyst DNA template); (iii) oocysts incubated in human ileocecal adenocarcinoma (HCT-8) cells (105–1 and 5 × 104–50); and (iv) diluted DNA template (5 × 104) from cell culture incubated parasites (×10–×1000).

Results

Serial dilutions of both cell culture and pure oocyst suspension DNA template yielded better linearity than cell culture derived standards, with dilutions of 106 oocysts exhibiting similar quantification cycle (Cq) values to those obtained from DNA template dilutions of 106 oocysts. In contrast, cell culture incubated oocysts demonstrated significantly higher DNA content than equivalent freely suspended oocysts and diluted DNA template from both cell culture derived and freely suspended oocysts across numerous concentrations.

Conclusions

For many studies involving Cryptosporidium, only relative DNA content is required and as such, the superior linearity afforded by freely suspended oocysts and diluted DNA template (from either cell culture derived standards or freely suspended oocysts) will allow for more accurate relative quantification in each assay. Parasite division in the cell culture standards likely explains the higher DNA content found. These standards, therefore, have the potential to more accurately reflect DNA content in cell culture assays, and despite more modern methods available for absolute quantification, i.e. droplet digital PCR (ddPCR), the ubiquity of qPCR for the foreseeable future encourages further investigation into the reduced linearity observed in these standards such as varying oocyst seeding density, non-linear growth rates and assay efficiency.
Comprehensive epigenome characterization reveals diverse transcriptional regulation across human vascular endothelial cells
Authors: Nakato Ryuichiro , Wada Youichiro , Nakaki Ryo , Nagae Genta , Katou Yuki , Tsutsumi Shuichi , Nakajima Natsu , Fukuhara Hiroshi , Iguchi Atsushi , Kohro Takahide , Kanki Yasuharu , Saito Yutaka , Kobayashi Mika , Izumi-Taguchi Akashi , Osato Naoki , Tatsuno Kenji , Kamio Asuka , Hayashi-Takanaka Yoko , Wada Hiromi , Ohta Shinzo , Aikawa Masanori , Nakajima Hiroyuki , Nakamura Masaki , McGee Rebecca C. , Heppner Kyle W. , Kawakatsu Tatsuo , Genno Michiru , Yanase Hiroshi , Kume Haruki , Senbonmatsu Takaaki , Homma Yukio , Nishimura Shigeyuki , Mitsuyama Toutai , Aburatani Hiroyuki , Kimura Hiroshi , Shirahige Katsuhiko
Published: December 2019

Background

Endothelial cells (ECs) make up the innermost layer throughout the entire vasculature. Their phenotypes and physiological functions are initially regulated by developmental signals and extracellular stimuli. The underlying molecular mechanisms responsible for the diverse phenotypes of ECs from different organs are not well understood.

Results

To characterize the transcriptomic and epigenomic landscape in the vascular system, we cataloged gene expression and active histone marks in nine types of human ECs (generating 148 genome-wide datasets) and carried out a comprehensive analysis with chromatin interaction data. We developed a robust procedure for comparative epigenome analysis that circumvents variations at the level of the individual and technical noise derived from sample preparation under various conditions. Through this approach, we identified 3765 EC-specific enhancers, some of which were associated with disease-associated genetic variations. We also identified various candidate marker genes for each EC type. We found that the nine EC types can be divided into two subgroups, corresponding to those with upper-body origins and lower-body origins, based on their epigenomic landscape. Epigenomic variations were highly correlated with gene expression patterns, but also provided unique information. Most of the deferentially expressed genes and enhancers were cooperatively enriched in more than one EC type, suggesting that the distinct combinations of multiple genes play key roles in the diverse phenotypes across EC types. Notably, many homeobox genes were differentially expressed across EC types, and their expression was correlated with the relative position of each organ in the body. This reflects the developmental origins of ECs and their roles in angiogenesis, vasculogenesis and wound healing.

Conclusions

This comprehensive analysis of epigenome characterization of EC types reveals diverse transcriptional regulation across human vascular systems. These datasets provide a valuable resource for understanding the vascular system and associated diseases.
Integrating Israeli Defense Force (IDF) veterans with disabilities into the workforce: characteristics and predictors
Authors: Segev Dan , Schiff Miriam
Published: December 2019

Background

According to the ICF Model, the central goal of rehabilitation is the returning of persons with disabilities to an active and fruitful life within society. The Israel Ministry of Defense Rehabilitation Department’s occupational rehabilitation program includes assessment, professional guidance, training, and assistance integrating into employment.

Aim

Examining predictors for the integration of Israel Defense Force veterans with disabilities into the workforce.

Methods

All 1416 male veterans with disabilities who served in the military, were injured during their service, and were treated by the Israel Ministry of Defense Rehabilitation Department between 2001 and 2006 were included in this study. Data collection was based on computerized administrative data in the Ministry of Defense. The data was collected with no identifying details.

Predictive variables were: health condition, personal factors, participation factors, level of functioning and structure, and variables relating to the local environment.

Results

Compared to a physical disability, mental and mixed (physical and mental) disabilities reduce the odds for integration into the workforce. Higher education at the time of the injury is an additional predictor for integration into the workforce. Participation in a rehabilitation track for further education to acquire a profession is one of the main predictors for integration into the workforce.

Conclusion

The results may enable developing more accurate intervention plans, with more efficient use of resources, including consolidation of existing information systems and monitoring the processes and outcomes of rehabilitation.
Energy harvesting and information transmission scheme with UAV relay cooperation
Authors: Ji Baofeng , Chen Zhenzhen , Li Yuqi , Chen Sudan , Zheng Guoqiang , Wen Hong
Published: December 2019

This paper proposed a system architecture model of two-hop unmanned aerial vehicle (UAV) relay wireless communication and designed an energy harvesting and information transmission algorithm based on the energy harvested by UAV relay node. The energy of nodes except source node can be obtained by energy harvesting and all the UAV relay nodes transmitted signals via power splitting. Under the advance of non-static channel, the information user nodes were configured with multiple antennas and adopted max ratio combination (MRC). Based on the optimization criterion of energy efficiency maximization, the analytical solution of the optimal power allocation scheme for energy harvested and information transmission of multi-user two-UAV relay system was derived in detail. Since the optimization problem was a non-convex problem, this paper adopted the high signal-to-noise ratio approximation method and the power splitting method to realize the closed-form solution expression. The optimal solution of the objective function subjected with constraints can be obtained by Lagrangian algorithm and Lambert W function. Finally, the proposed algorithms and theoretical analysis are verified by simulations.
Expression of Jerusalem artichoke (Helianthus tuberosus L.) fructosyltransferases, and high fructan accumulation in potato tubers
Authors: Moon Ki-Beom , Ko Hyunjun , Park Ji-Sun , Sohn Jung-Hoon , Cho Hye-Sun , Park Youn-il , Kim Hyun-Soon , Jeon Jae-Heung
Published: December 2019

Fructans are polymers of fructose that are present as storage carbohydrates in various plants. Jerusalem artichoke (Helianthus tuberosus L.) contains a high amount of inulin. Two enzymes are involved in inulin biosynthesis. The sucrose:sucrose 1-fructosyltransferase (1-SST) enzyme mainly catalyzes the synthesis of 1-kestose from sucrose. In the next step, fructan:fructan 1-fructosyltransferase (1-FFT) catalyzes the synthesis of inulin from 1-kestose. In this study, the Ht1-SST and Ht1-FFT genes were isolated from Jerusalem artichoke and expressed in potato (Solanum tuberosum L.), either separately or together, via Agrobacterium-mediated transformation. Transgenic potato tubers overexpressing Ht1-SST accumulated 1-kestose to a high level (up to 3.36 mg/g), while tubers overexpressing both Ht1-SST and Ht1-FFT accumulated up to 3.14 mg/g short-chain inulin-type fructans, with the degree of polymerization (DP) ranging from 3 to 5, excluding high DP inulins. Transgenic potato plants accumulated fructo-oligosaccharides to a high level, following the fructan biosynthetic pathway of Jerusalem artichoke, and therefore present a high potential for the mass production of inulin through established potato breeding and cultivation methods.
PTSD prevalence among resident mothers and their offspring in Rwanda 25 years after the 1994 genocide against the Tutsi
Authors: Mutuyimana Celestin , Sezibera Vincent , Nsabimana Epaphrodite , Mugabo Lambert , Cassady Cindi , Musanabaganwa Clarisse , Kayiteshonga Yvonne
Published: December 2019

Background

The 1994 Genocide against the Tutsi was a major traumatic event affecting nearly all Rwandans. Significant psychological sequels continue to occur in the population 25 years after, with a high prevalence of posttraumatic stress disorder (PTSD) found in women. Three groups are typically designated with regard to the Genocide against the Tutsi: those who were targeted and categorized as genocide “survivors,” those who were in the country during the genocide and were the “non-targeted” group, and those who were outside of the country, referred to as the “1959 returnees.” Each group experienced various traumatic events during and in the aftermath of the genocide. Offspring of the designated groups, currently exhibit symptoms of PTSD disregarding of being born in the years following the genocide. A number of studies have described the prevalence of PTSD in the general adult population. There is a lack of research comparing the prevalence of PTSD in women and their offspring among these three target groups, therefore, this study aimed to bridge the gap.

Methods

We conducted a comparative cross-sectional study with a sample of 432 mothers and 432 children in three categories: genocide survivors, in country non-targeted and 1959 returnees. Participant ages for children were between 14 to 22 years and for mothers, between the ages of 32 to 87 years. The UCLA-PTSD DSM-5, PTSD Check list-5 and Life events Checklist-5 were translated from English to Kinyarwanda and were used to assess exposure to trauma and the prevalence of PTSD symptoms in Rwandan mothers and their offspring.

Results

Key Results yield a PTSD rate of 18.8, 6.2, 5.2% within survivors, in country non-targeted, and returnees respectively with an average PTSD rate of 43.8% for parents, and 16.5% for offspring.

Conclusion

PTSD among the mothers’ groups and their offspring have been found, specifically in the offspring of genocide survivors. Considering these adolescents were not born at the time of the 1994 Genocide against the Tutsi, the results suggest future studies should explore the precipitating factors contributing to the PTSD symptoms within this specific group.
Evaluation of immunological, inflammatory, and oxidative stress biomarkers in gasoline station attendants
Authors: Moro Angela Maria , Sauer Elisa , Brucker Natália , Charão Mariele Feiffer , Gauer Bruna , do Nascimento Sabrina Nunes , Goethel Gabriela , Duarte Marta Maria Medeiros Frescura , Garcia Solange Cristina
Published: December 2019

Background

Gasoline is a complex mixture of saturated and unsaturated hydrocarbons, in which aromatic compounds, such as BTX (benzene, toluene, and xylene) feature as the main constituents. Simultaneous exposure to these aromatic hydrocarbons causes a significant impact on benzene toxicity. In order to detect early alterations caused in gasoline station attendants exposed to BTX compounds, immunological, inflammatory, and oxidative stress biomarkers were evaluated.

Methods

A total of 66 male subjects participated in this study. The gasoline station attendants (GSA) group consisted of 38 gasoline station attendants from Rio Grande do Sul, Brazil. The non-exposed group consisted of 28 subjects who were non-smokers and who had no history of occupational exposure. Environmental and biological monitoring of BTX exposure was performed using blood and urine.

Results

The GSA group showed increased BTX concentrations in relation to the non-exposed group (p < 0.001). The GSA group showed elevated protein carbonyl (PCO) levels and pro-inflammatory cytokines, decreased expression of CD80 and CD86 in monocytes, and reduced glutathione S-transferase (GST) activity compared to the non-exposed group (p < 0.05). BTX levels and trans,trans-muconic acid levels were positively correlated with pro-inflammatory cytokines and negatively correlated with interleukin-10 contents (p < 0.001). Increased levels of pro-inflammatory cytokines were accompanied by increased PCO contents and decreased GST activity (p < 0.001). Furthermore, according to the multiple linear regression analysis, benzene exposure was the only factor that significantly contributed to the increased pro-inflammatory cytokines (p < 0.05).

Conclusions

Taken together, these findings show the influence of exposure to BTX compounds, especially benzene, on the immunological, inflammatory, and oxidative stress biomarkers evaluated. Furthermore, the data suggest the relationship among the evaluated biomarkers of effect, which could contribute to providing early signs of damage to biomolecules in subjects occupationally exposed to BTX compounds.
Gamma-hexalactone flavoring causes DNA lesion and modulates cytokines secretion at non-cytotoxic concentrations
Authors: Zuravski Luísa , Escobar Taiane A. , Schmitt Elizandra G. , Amaral Queila D. F. , Paula Fávero R. , Duarte Thiago , Duarte Marta M. M. F. , Machado Michel M. , Oliveira Luís F. S. , Manfredini Vanusa
Published: December 2019

Background

The γ-hexalactone is a flavoring agent for alcoholic beverages, teas, breads, dairy products, coffees, buttery products among others. It presents low molecular weight and exhibits sweet fruity aroma with nuances of nuts. As far as we know, both literature and government regulations have gaps regarding the safe use of the γ-hexalactone. In this context, the main objective of this work was to evaluate the effects of γ-hexalactone through in silico and in vitro approaches.

Methods

The in silico analysis was performed through four free online platforms (admetSAR, Osiris Property Explorer®, pkCSM platform and PreADMET) and consisted of comparative structural analysis with substances present in databases. The computational prediction was performed in the sense of complement and guide the in vitro tests. Regarding in vitro investigations, screening of cytotoxicity (assessed by cell proliferation and viability parameters) in lymphocytes exposed to γ-hexalactone for 72 h were carried out previously to determine non-cytotoxic concentrations. Following this screening, concentrations of 5.15, 0.515, and 0.0515 μM were selected for the study of the respective potentials: genotoxic (assessed by DNA comet assay), chromosomal mutation (analysis of micronucleus frequency) and immunomodulatory (cytokine quantification using ELISA immunoassay). The results of in vitro assays were compared by one-way analysis of variance (ANOVA), followed by Bonferroni’s post hoc test, conducted by statistic software.

Results

The platform PreADMET pointed out that γ-hexalactone is potentially mutagenic and carcinogenic. The comet assay data corroborate with these results demonstrating that γ-hexalactone at 5.15 μM caused lymphocytes DNA damage. In relation to cytokine secretion, the results indicate that lymphocytes were activated by γ-hexalactone at non-cytotoxic concentrations, involving an increase in the IL-1 levels in all tested concentrations, ranging from approximately 56 to 93%. The γ-hexalactone only at 5.15 μM induced increase in the levels of IL-6 (~ 60%), TNF-α (~ 68%) and IFN-γ (~ 29%), but decreased IL-10 (~ 46%) in comparison with the negative control (p < 0.05). No change was observed in total lymphocytes or in cell viability at the concentrations tested.

Conclusions

In summary, the γ-hexalactone demonstrated immunomodulatory and genotoxic effects at non-cytotoxic concentrations in healthy lymphocytes.
Polarizing receptor activation dissociates fibroblast growth factor 2 mediated inhibition of myelination from its neuroprotective potential
Authors: Thümmler Katja , Rom Eran , Zeis Thomas , Lindner Maren , Brunner Sarah , Cole John J. , Arseni Diana , Mücklisch Steve , Edgar Julia M. , Schaeren-Wiemers Nicole , Yayon Avner , Linington Christopher
Published: December 2019

Fibroblast growth factor (FGF) signaling contributes to failure of remyelination in multiple sclerosis, but targeting this therapeutically is complicated by its functional pleiotropy. We now identify FGF2 as a factor up-regulated by astrocytes in active inflammatory lesions that disrupts myelination via FGF receptor 2 (FGFR2) mediated activation of Wingless (Wnt) signaling; pharmacological inhibition of Wnt being sufficient to abrogate inhibition of myelination by FGF2 in tissue culture. Using a novel FGFR1-selective agonist (F2 V2) generated by deleting the N-terminal 26 amino acids of FGF2 we demonstrate polarizing signal transduction to favor FGFR1 abrogates FGF mediated inhibition of myelination but retains its ability to induce expression of pro-myelinating and immunomodulatory factors that include Cd93, Lif, Il11, Hbegf, Cxcl1 and Timp1. Our data provide new insights into the mechanistic basis of remyelination failure in MS and identify selective activation of FGFR1 as a novel strategy to induce a neuroprotective signaling environment in multiple sclerosis and other neurological diseases.
Organotypic slice culture model demonstrates inter-neuronal spreading of alpha-synuclein aggregates
Authors: Elfarrash Sara , Jensen Nanna Møller , Ferreira Nelson , Betzer Cristine , Thevathasan Jervis Vermal , Diekmann Robin , Adel Mohamed , Omar Nisreen Mansour , Boraie Mohamed Z. , Gad Sabry , Ries Jonas , Kirik Deniz , Nabavi Sadegh , Jensen Poul Henning
Published: December 2019

Here we describe the use of an organotypic hippocampal slice model for studying α-synuclein aggregation and inter-neuronal spreading initiated by microinjection of pre-formed α-synuclein fibrils (PFFs). PFF injection at dentate gyrus (DG) templates the formation of endogenous α-synuclein aggregates in axons and cell bodies of this region that spread to CA3 and CA1 regions. Aggregates are insoluble and phosphorylated at serine-129, recapitulating Lewy pathology features found in Parkinson’s disease and other synucleinopathies. The model was found to favor anterograde spreading of the aggregates. Furthermore, it allowed development of slices expressing only serine-129 phosphorylation-deficient human α-synuclein (S129G) using an adeno-associated viral (AAV) vector in α-synuclein knockout slices. The processes of aggregation and spreading of α-synuclein were thereby shown to be independent of phosphorylation at serine-129. We provide methods and highlight crucial steps for PFF microinjection and characterization of aggregate formation and spreading. Slices derived from genetically engineered mice or manipulated using viral vectors allow testing of hypotheses on mechanisms involved in the formation of α-synuclein aggregates and their prion-like spreading.