bluuebunny/crossref_metadata_2025_split huggingface dataset:
4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol)‐induced melanocyte cytotoxicity is enhanced by UVB exposure through generation of oxidative stress
Authors: Goto Noriko , Tsujimoto Mariko , Nagai Hiroshi , Masaki Taro , Ito Shosuke , Wakamatsu Kazumasa , Nishigori Chikako 
Published: April 2018

Abstract4‐(4‐Hydroxyphenyl)‐2‐butanol (rhododendrol, RD), a skin‐whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity‐dependent manner. We examined the effect of UV radiation (UVR) on RD‐induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD‐induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N‐acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress‐induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl‐RD‐catechol and RD‐pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS‐generating substances and that the tendency to produce RD‐pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD‐induced leukoderma and provide information for innovation of safe skin‐whitening compounds.
PR‐10 proteins as potential mediators of melatonin‐cytokinin cross‐talk in plants: crystallographic studies of LlPR‐10.2B isoform from yellow lupine
Authors: Sliwiak Joanna , Sikorski Michal , Jaskolski Mariusz 
Published: April 2018

LlPR‐10.2B, a Pathogenesis‐related class 10 (PR‐10) protein from yellow lupine (Lupinus luteus) was crystallized in complex with melatonin, an emerging important plant regulator and antioxidant. The structure reveals two molecules of melatonin bound in the internal cavity of the protein, plus a very well‐defined electron density near the cavity entrance, corresponding to an unknown ligand molecule comprised of two flat rings, which is most likely a product of melatonin transformation. In a separate LlPR‐10.2B co‐crystallization experiment with an equimolar mixture of melatonin and trans‐zeatin, which is a cytokinin phytohormone well recognized as a PR‐10‐binding partner, a quaternary 1 : 1 : 1 : 1 complex was formed, in which one of the melatonin‐binding sites has been substituted with trans‐zeatin, whereas the binding of melatonin at the second binding site and binding of the unknown ligand are undisturbed. This unusual complex, when compared with the previously described PR‐10/trans‐zeatin complexes and with the emerging structural information about melatonin binding by PR‐10 proteins, provides intriguing insights into the role of PR‐10 proteins in phytohormone regulation in plants, especially with the involvement of melatonin, and implicates the PR‐10 proteins as low‐affinity melatonin binders under the conditions of elevated melatonin concentration.DatabasesAtomic coordinates and processed structure factors corresponding to the final models of the LlPR‐10.2B/melatonin and LlPR‐10.2B/melatonin + trans‐zeatin complexes have been deposited with the Protein Data Bank (PDB) under the accession codes 5MXB and 5MXW. The corresponding raw X‐ray diffraction images have been deposited in the RepOD Repository at the Interdisciplinary Centre for Mathematical and Computational Modelling (ICM) of the University of Warsaw, Poland, and are available for download with the following Digital Object Identifiers (DOI): https://doi.org/10.18150/repod.9923638 and https://doi.org/10.18150/repod.6621013.
Comparison of hyperspectral classification methods for the analysis of cerium oxide nanoparticles in histological and aqueous samples
Authors: IDELCHIK M.P.S. , DILLON J. , ABARIUTE L. , GUTTENBERG M.A. , SEGARCEANU A. , NEU‐BAKER N.M. , BRENNER S.A. 
Published: April 2018

SummaryHyperspectral imaging (HSI) and classification are established methods that are being applied in new ways to the analysis of nanoscale materials in a variety of matrices. Typically, enhanced darkfield microscopy (EDFM)‐based HSI data (also known as image datacubes) are collected in the wavelength range of 400–1000 nm for each pixel in a datacube. Utilising different spectral library (SL) creation methods, spectra from pixels in the datacube corresponding to known materials can be collected into reference spectral libraries (RSLs), which can be used to classify materials in datacubes of experimental samples using existing classification algorithms. In this study, EDFM‐HSI was used to visualise and analyse industrial cerium oxide (CeO2; ceria) nanoparticles (NPs) in rat lung tissues and in aqueous suspension. Rats were exposed to ceria NPs via inhalation, mimicking potential real‐world occupational exposures. The lung tissues were histologically prepared: some tissues were stained with hematoxylin and eosin (H&E) and some were left unstained. The goal of this study was to determine how HSI and classification results for ceria NPs were influenced by (1) the use of different RSL creation and classification methods and (2) the application of those methods to samples in different matrices (stained tissue, unstained tissue, or aqueous solution). Three different RSL creation methods – particle filtering (PF), manual selection, and spectral hourglass wizard (SHW) – were utilised to create the RSLs of known materials in unstained and stained tissue, and aqueous suspensions, which were then used to classify the NPs in the different matrices. Two classification algorithms – spectral angle mapper (SAM) and spectral feature fitting (SFF) – were utilised to determine the presence or absence of ceria NPs in each sample. The results from the classification algorithms were compared to determine how each influenced the classification results for samples in different matrices. The results showed that sample matrix and sample preparation significantly influenced the NP classification thresholds in the complex matrices. Moreover, considerable differences were observed in the classification results when utilising each RSL creation and classification method for each type of sample. Results from this study illustrate the importance of appropriately selecting HSI algorithms based on specific material and matrix characteristics in order to obtain optimal classification results. As HSI is increasingly utilised for NP characterisation for clinical, environmental and health and safety applications, this investigation is important for further refining HSI protocols while ensuring appropriate data collection and analysis.
Clinical evaluation of efficacy, tolerability and pharmacokinetics of yimitasvir phosphate in patients infected with hepatitis C virus
Authors: Zhang Hong , Zhu Xiaoxue , Li Qingmei , Lou Jinfeng , Sun Jixuan , Shen Zhenwei , Chen Hong , Li Xiaojiao , Wu Min , Li Cuiyun , Liu Jingrui , Liu Chengjiao , Hu Yue , Wang Jing , Chen Guiling , Ding Yanhua , Niu Junqi 
Published: April 2018

Abstract

Objective
Yimitasvir phosphate, an inhibitor of nonstructural protein 5A (NS5A) replication complex of hepatitis C virus (HCV), was evaluated in a double-blind, placebo-controlled, parallel, multiple-dose study.

Methods
Twenty-four patients with chronic HCV genotype 1 infection were randomized to receive a 7-day course of yimitasvir phosphate at daily doses of 30, 100 or 200 mg or placebo. Antiviral efficacy, resistance profile, pharmacokinetics (PK), safety and tolerability were assessed.

Key findings
The maximal reduction in HCV RNA from baseline was 5.17 log10 IU/ml. However, most patients experienced viral rebound on or before day 3 after yimitasvir treatment was initiated. The PK profile revealed median peak plasma concentrations at 4–12 h postdose and a mean terminal half-life of 14.47–17.09 h, the basis for daily dosing. Steady drug state was achieved following 5 days of daily dosing. The accumulation rate was low (1.29–1.73). There were no significant alterations in vital signs and laboratory findings among all participants.

Conclusions
This study shows that yimitasvir phosphate was well tolerated, and the PK profile supported daily dosing regimens. A 1-week (7-day) treatment course led to a quick and significant reduction in HCV RNA level in this cohort with HCV GT-1 infection.
Analysis of the first‐time pass rate of the American College of Veterinary Emergency and Critical Care certifying examination (2010–2015)
Authors: Jandrey Karl E. , Goggs Robert , Kerl Marie , Guillaumin Julien , Kent Michael S. 
Published: April 2018

AbstractObjectivesTo disseminate information regarding the annual pass rates for the American College of Veterinary Emergency and Critical Care (ACVECC) certifying examination. To compare the first‐time pass rates (FTPR) of ACVECC residents trained in academic and private practice settings.DesignRetrospective study.SettingACVECC examination.AnimalsNone.InterventionsNone.Measurements and Main ResultsAnonymized ACVECC examination performance data from 2010–2015 inclusive were analyzed. Overall pass rates and FTPR were calculated for all candidates and categorized by type of residency training program. The overall pass rate for all candidates was 64.3%. The median pass rate for the 6‐year period was 63.8% [IQR 59.3–67.3%]. The FTPR for residents trained in academic programs was significantly higher than for residents trained in private practice (77.1% vs 47.2%,P< 0.0001). When residents were subdivided by species‐focus of training program, there was no significant difference between academic versus private practice training programs for large‐animal candidates (P= 0.2), but there remained a significant difference between residency training programs for small‐animal candidates (P< 0.0001).ConclusionsBetween 2010 and 2015 residents trained in academic training programs were significantly more likely to pass the ACVECC certifying examination compared to those trained in private practice training programs. The causes of this difference are uncertain, are likely multifactorial and warrant further investigation.
The independence polynomial of conjugate graph and noncommuting graph of groups of small order.
Authors: Najmuddin Nabilah , Sarmin Nor Haniza , Erfanian Ahmad 
Published: April 2018

An independent set of a graph is a set of pairwise non-adjacent vertices. The independence polynomial of a graph is defined as a polynomial in which the coefficient is the number of the independent set in the graph. Meanwhile, a graph of a group G is called conjugate graph if the vertices are non-central elements of G and two distinct vertices are adjacent if they are conjugate. The noncommuting graph is defined as a graph whose vertex set is non-central elements in which two vertices are adjacent if and only if they do not commute. In this research, the independence polynomial of the conjugate graph and noncommuting graph are found for three nonabelian groups of order at most eight.
Improvement of estimation based on small number of events per variable (EPV) using bootstrap logistics regression model
Authors: Lola Muhamad Safiih , Zainuddin Nurul Hila , Ramlee Mohd Noor Afiq , Abdul Rahman Muhamad Na’eim , Abdullah Mohd Tajuddin 
Published: April 2018

In this research, a bootstrap approach model is proposed, namely as Bootstrap Logistics Regression Model (BLRM) that is specifically used to solve the small events per variable (EPV) problem. Considering a sample data from study case of endemic dengue at several localities in Kelantan, Malaysia, a simulation study is conducted. We generated 5, 10, 20 and 25 mean samples with 500 times replacement, 1500 times bootstrap for each small EPV value (EPV= 2, 3, 4 and 5) according to the basic reproduction number, R0 for endemic dengue. The performance of the propose BLRM revealed that the frequency distribution of estimated regression coefficient became less peaked and possessed thinner tails; the average percent relative bias consistently decreased and was closed to true parameter; the sample variance (MSE and RMSE) of the estimated regression coefficients of were smaller than original model.
Polycyclic transformations of crystallographic groups with quaternion point group of order eight
Authors: Mohammad Siti Afiqah , Sarmin Nor Haniza , Mat Hassim Hazzirah Izzati 
Published: April 2018

Exploration of a group's properties is vital for better understanding about the group. Amongst other properties, the homological invariants including the nonabelian tensor square of a group can be explicated by showing that the group is polycyclic. In this paper, the polycyclic presentations of certain crystallographic groups with quaternion point group of order eight are shown to be consistent; which implies that these groups are polycyclic.
Alterations of Metabolic and Lipid Profiles in Polymyxin-Resistant Pseudomonas aeruginosa
Authors: Han Mei-Ling , Zhu Yan , Creek Darren J. , Lin Yu-Wei , Anderson Dovile , Shen Hsin-Hui , Tsuji Brian , Gutu Alina D. , Moskowitz Samuel M. , Velkov Tony , Li Jian 
Published: April 2018

ABSTRACT

Multidrug-resistant
Pseudomonas aeruginosa
presents a global medical challenge, and polymyxins are a key last-resort therapeutic option. Unfortunately, polymyxin resistance in
P. aeruginosa
has been increasingly reported. The present study was designed to define metabolic differences between paired polymyxin-susceptible and -resistant
P. aeruginosa
strains using untargeted metabolomics and lipidomics analyses. The metabolomes of wild-type
P. aeruginosa
strain K ([PAK] polymyxin B MIC, 1 mg/liter) and its paired
pmrB
mutant strains, PAK
pmrB6
and PAK
pmrB12
(polymyxin B MICs of 16 mg/liter and 64 mg/liter, respectively) were characterized using liquid chromatography-mass spectrometry, and metabolic differences were identified through multivariate and univariate statistics. PAK
pmrB6
and PAK
pmrB12
, which displayed lipid A modifications with 4-amino-4-deoxy-
l
-arabinose, showed significant perturbations in amino acid and carbohydrate metabolism, particularly the intermediate metabolites from 4-amino-4-deoxy-
l
-arabinose synthesis and the methionine salvage cycle pathways. The genomics result showed a premature termination (Y275stop) in
speE
(encoding spermidine synthase) in PAK
pmrB6
, and metabolomics data revealed a decreased intracellular level of spermidine in PAK
pmrB6
compared to that in PAK
pmrB12
. Our results indicate that spermidine may play an important role in high-level polymyxin resistance in
P. aeruginosa
. Interestingly, both
pmrB
mutants had decreased levels of phospholipids, fatty acids, and acyl-coenzyme A compared to those in the wild-type PAK. Moreover, the more resistant PAK
pmrB12
mutant exhibited much lower levels of phospholipids than the PAK
pmrB6
mutant, suggesting that the decreased phospholipid level was associated with polymyxin resistance. In summary, this study provides novel mechanistic information on polymyxin resistance in
P. aeruginosa
and highlights its impacts on bacterial metabolism.
Are Sphingolipids and Serine Dipeptide Lipids Underestimated Virulence Factors of Porphyromonas gingivalis?
Authors: Olsen Ingar , Nichols Frank C. 
Published: April 2018

ABSTRACT

The keystone periodontal pathogen
Porphyromonas gingivalis
produces phosphorylated dihydroceramide lipids (sphingolipids) such as phosphoethanolamine dihydroceramide (PE DHC) and phosphoglycerol dihydroceramide (PG DHC) lipids. Phosphorylated DHCs (PDHCs) from
P. gingivalis
can affect a number of mammalian cellular functions, such as potentiation of prostaglandin secretion from gingival fibroblasts, promotion of RANKL-induced osteoclastogenesis, promotion of apoptosis, and enhancement of autoimmunity. In
P. gingivalis
, these lipids affect anchoring of surface polysaccharides, resistance to oxidative stress, and presentation of surface polysaccharides (anionic polysaccharides and K-antigen capsule). In addition to phosphorylated dihydroceramide lipids, serine dipeptide lipids of
P. gingivalis
are implicated in alveolar bone loss in chronic periodontitis through interference with osteoblast differentiation and function and promotion of osteoclast activity. As a prerequisite for designation as bacterial virulence factors, bacterial sphingolipids and serine dipeptide lipids are recovered in gingival/periodontal tissues, tooth calculus, human blood, vascular tissues, and brain. In addition to
P. gingivalis
, other bacteria of the genera
Bacteroides
,
Parabacteroides
,
Porphyromonas
,
Tannerella
, and
Prevotella
produce sphingolipids and serine dipeptide lipids. The contribution of PDHCs and serine dipeptide lipids to the pathogenesis of periodontal and extraoral diseases may be an underappreciated area in microbe-host interaction and should be more intensively investigated.
Use of Automated Urine Microscopy Analysis in Clinical Diagnosis of Urinary Tract Infection: Defining an Optimal Diagnostic Score in an Academic Medical Center Population
Authors: Foudraine Dimard E. , Bauer Martijn P. , Russcher Anne , Kusters Elske , Cobbaert Christa M. , van der Beek Martha T. , Stalenhoef Janneke E. 
Published: April 2018

ABSTRACT
A retrospective case record study was conducted that established a scoring tool based on clinical and iQ200 parameters, able to predict or rule out the clinical diagnosis of UTI in the majority of adult patients in an academic hospital. Automated standardized quantitative urine analysis, such as iQ200 analysis, is on the rise because of its high accuracy and efficiency compared to those of traditional urine analysis. Previous research on automated urinalysis focused mainly on predicting culture results but not on the clinical diagnosis of urinary tract infection (UTI). A retrospective analysis was conducted of consecutive urine samples sent in for culture because of suspected UTI. UTI was defined by expert opinion, based on reported symptoms, conventional urine sediment analysis, and urine cultures. Parameters of iQ200 analysis and clinical symptoms and signs were compared between cases and controls. Optimal cutoff values were determined for iQ200 parameters, and multivariate logistic regression analysis was used to identify the set of variables that best predicts the clinical diagnosis of UTI for development of a scoring tool. A total of 382 patients were included. Optimal cutoff values of iQ200 analysis were 74 white blood cells (WBC)/μl, 6,250 “all small particles” (ASP)/μl, and a bacterial score of 2 on an ordinal scale of 0 to 5. The scoring tool attributed 1 point for frequent micturition or increased urge, 2 points for dysuria, 1 point for a bacterial score of ≥2, 2 points for WBC/μl of ≥50, and an additional point for WBC/μl of ≥150. This score had a sensitivity of 86% and a specificity of 92% when using a threshold of <4 points. The combination of iQ200 analysis and a simple survey could predict or rule out UTIs in a majority of patients in an academic medical center.
Kaposi's Sarcoma-Associated Herpesvirus mRNA Accumulation in Nuclear Foci Is Influenced by Viral DNA Replication and Viral Noncoding Polyadenylated Nuclear RNA
Authors: Vallery Tenaya K. , Withers Johanna B. , Andoh Joana A. , Steitz Joan A. 
Published: April 2018

ABSTRACT
Kaposi's sarcoma-associated herpesvirus (KSHV), like other herpesviruses, replicates within the nuclei of its human cell host and hijacks host machinery for expression of its genes. The activities that culminate in viral DNA synthesis and assembly of viral proteins into capsids physically concentrate in nuclear areas termed viral replication compartments. We sought to better understand the spatiotemporal regulation of viral RNAs during the KSHV lytic phase by examining and quantifying the subcellular localization of select viral transcripts. We found that viral mRNAs, as expected, localized to the cytoplasm throughout the lytic phase. However, dependent on active viral DNA replication, viral transcripts also accumulated in the nucleus, often in foci in and around replication compartments, independent of the host shutoff effect. Our data point to involvement of the viral long noncoding polyadenylated nuclear (PAN) RNA in the localization of an early, intronless viral mRNA encoding ORF59-58 to nuclear foci that are associated with replication compartments.

IMPORTANCE
Late in the lytic phase, mRNAs from Kaposi's sarcoma-associated herpesvirus accumulate in the host cell nucleus near viral replication compartments, centers of viral DNA synthesis and virion production. This work contributes spatiotemporal data on herpesviral mRNAs within the lytic host cell and suggests a mechanism for viral RNA accumulation. Our findings indicate that the mechanism is independent of the host shutoff effect and splicing but dependent on active viral DNA synthesis and in part on the viral noncoding RNA, PAN RNA. PAN RNA is essential for the viral life cycle, and its contribution to the nuclear accumulation of viral messages may facilitate propagation of the virus.
Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles
Authors: Brown Christopher T. , Xiong Weili , Olm Matthew R. , Thomas Brian C. , Baker Robyn , Firek Brian , Morowitz Michael J. , Hettich Robert L. , Banfield Jillian F. 
Published: April 2018

ABSTRACT
During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.

IMPORTANCE
Humans are colonized by microbes at birth, a process that is important to health and development. However, much remains to be known about the fine-scale microbial dynamics that occur during the colonization period. We conducted a genome-resolved study of microbial community composition, replication rates, and proteomes during the first 3 months of life of both healthy and sick premature infants. Infants were found to be colonized by similar microbes, but each underwent a distinct colonization trajectory. Interestingly, related microbes colonizing different infants were found to have distinct proteomes, indicating that microbiome function is not only driven by which organisms are present, but also largely depends on microbial responses to the unique set of physiological conditions in the infant gut.