bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial Degradation of Nicotinamide by a Strain Alcaligenes sp. P156
Authors: Hu Chunhui , Zhao Shuxue , Li Kuiran , Yu Hao 
Published: March 2019

AbstractA novel Alcaligenes sp. strain P156, which can utilize nicotinamide as its sole source of carbon, nitrogen and energy, was enriched and isolated from soil in a solid waste treatment plant. Aerobic growth and degradation with nicotinamide were characterized. Seven nicotinamide degradation-related genes were obtained by sequence alignment from the genome sequence of strain P156. Four genes, designated naaA, naaD, naaE and naaF, were cloned and heterologously expressed. Nicotinamide degradation is initiated by deamination to form nicotinic acid catalyzed by the nicotinamidase NaaA, which shares highest amino acid sequence identity (27.2%) with nicotinamidase from Arabidopsis thaliana. Nicotinic acid is converted to 6-hydroxynicotinic acid, which is further oxidized to 2,5-dihydroxypyridine (2,5-DHP). 2,5-DHP is then transformed to a ring-cleavage product, N-formylmaleamic acid, by an Fe2+ dependent dioxygenase NaaD. N-formylmaleamic acid is transformed to fumaric acid through maleamic acid and maleic acid by NaaE and NaaF, respectively. To our knowledge, this is the first report of the complete microbial degradation of nicotinamide in bacteria. Nicotinamide is considered as a model compound for the study of microbial degradation of pyridinic compounds, and the nicotinamide degrading related genes in strain P156 were distributed differently from the reported similar gene clusters. Therefore, this study contribute to the knowledge on the degradation of pyridinic compounds.
Allele-specific expression variation at different ploidy levels in Squalius alburnoides
Authors: Matos Isa , Machado Miguel P. , Schartl Manfred , Coelho Maria Manuela 
Published: March 2019

AbstractAllopolyploid plants are long known to be subject to a homoeolog expression bias of varying degree. The same phenomenon was only much later suspected to occur also in animals based on studies of single selected genes in an allopolyploid vertebrate, the Iberian fish Squalius alburnoides. Consequently, this species became a good model for understanding the evolution of gene expression regulation in polyploid vertebrates. Here, we analyzed for the first time genome-wide allele-specific expression data from diploid and triploid hybrids of S. alburnoides and compared homoeolog expression profiles of adult livers and of juveniles. Co-expression of alleles from both parental genomic types was observed for the majority of genes, but with marked homoeolog expression bias, suggesting homoeolog specific reshaping of expression level patterns in hybrids. Complete silencing of one allele was also observed irrespective of ploidy level, but not transcriptome wide as previously speculated. Instead, it was found only in a restricted number of genes, particularly ones with functions related to mitochondria and ribosomes. This leads us to hypothesize that allelic silencing may be a way to overcome intergenomic gene expression interaction conflicts, and that homoeolog expression bias may be an important mechanism in the achievement of sustainable genomic interactions, mandatory to the success of allopolyploid systems, as in S. alburnoides.
Poly ADP ribosylation and extracellular vesicle activity in rod photoreceptor degeneration
Authors: Vidal-Gil Lorena , Sancho-Pelluz Javier , Zrenner Eberhart , Oltra Maria , Sahaboglu Ayse 
Published: March 2019

AbstractRetinitis Pigmentosa is a group of inherited neurodegenerative diseases that result in selective cell death of photoreceptors. In the developed world, RP is regarded as the main cause of blindness among the working age population. The precise mechanisms eventually leading to cell death remain unknown and to date no adequate treatment for RP is available. Poly ADP ribose polymerase (PARP) over activity is involved in photoreceptor degeneration and pharmacological inhibition or genetic knock-down PARP1 activity protect photoreceptors in mice models, the mechanism of neuroprotection is not clear yet. Our result indicated that olaparib, a PARP1 inhibitor, significantly rescued photoreceptor cells in rd10 retina. Extracellular vesicles (EVs) were previously recognized as a mechanism for discharging useless cellular components. Growing evidence has elucidated their roles in cell–cell communication by carrying nucleic acids, proteins and lipids that can, in turn, regulate behavior of the target cells. Recent research suggested that EVs extensively participate in progression of diverse blinding diseases, such as age-related macular (AMD) degeneration. Our study demonstrates the involvement of EVs activity in the process of photoreceptor degeneration in a PDE6 mutation. PARP inhibition protects photoreceptors via regulation of the EVs activity in rod photoreceptor degeneration in a PDE6b mutation.
Proteolytic Degradation of reduced Human Beta Defensin 1 generates a Novel Antibiotic Octapeptide
Authors: Wendler Judith , Schroeder Bjoern O. , Ehmann Dirk , Koeninger Louis , Mailänder-Sánchez Daniela , Lemberg Christina , Wanner Stephanie , Schaller Martin , Stange Eduard F. , Malek Nisar P. , Weidenmaier Christopher , LeibundGut-Landmann Salomé , Wehkamp Jan 
Published: March 2019

AbstractMicrobial resistance against clinical used antibiotics is on the rise. Accordingly, there is a high demand for new innovative antimicrobial strategies. The host-defense peptide human beta-defensin 1 (hBD-1) is produced continuously by epithelial cells and exhibits compelling antimicrobial activity after reduction of its disulphide bridges. Here we report that proteolysis of reduced hBD-1 by gastrointestinal proteases as well as human duodenal secretions produces an eight-amino acid carboxy-terminal fragment. The generated octapeptide retains antibiotic activity, yet with distinct characteristics differing from the full-length peptide. We modified the octapeptide by stabilizing its termini and by using non-natural D-amino acids. The native and modified peptide variants showed antibiotic activity against pathogenic as well as antibiotic-resistant microorganisms, including E. coli, P. aeruginosa and C. albicans. Moreover, in an in vitro C. albicans infection model the tested peptides demonstrated effective amelioration of C. albicans infection without showing cytotoxity on human cells. In summary, protease degradation of hBD-1 provides a yet unknown mechanism to broaden antimicrobial host defense, which could be used to develop defensin-derived therapeutic applications.
Cyclosporin A ameliorates cerebral oxidative metabolism and infarct size in the endothelin-1 rat model of transient cerebral ischaemia
Authors: Forsse Axel , Nielsen Troels Halfeld , Nygaard Kevin Heebøll , Nordström Carl-Henrik , Gramsbergen Jan Bert , Poulsen Frantz Rom 
Published: March 2019

AbstractCerebral microdialysis can be used to detect mitochondrial dysfunction, a potential target of neuroprotective treatment. Cyclosporin A (CsA) is a mitochondrial stabiliser that in a recent clinical stroke trial showed protective potential in patients with successful recanalisation. To investigate specific metabolic effects of CsA during reperfusion, and hypothesising that microdialysis values can be used as a proxy outcome measure, we assessed the temporal patterns of cerebral energy substrates related to oxidative metabolism in a model of transient focal ischaemia. Transient ischaemia was induced by intracerebral microinjection of endothelin-1 (150 pmol/15 µL) through stereotaxically implanted guide cannulas in awake, freely moving rats. This was immediately followed by an intravenous injection of CsA (NeuroSTAT; 15 mg/kg) or placebo solution during continuous microdialysis monitoring. After reperfusion, the lactate/pyruvate ratio (LPR) was significantly lower in the CsA group vs placebo (n = 17, 60.6 ± 24.3%, p = 0.013). Total and striatal infarct volumes (mm3) were reduced in the treatment group (n = 31, 61.8 ± 6.0 vs 80.6 ± 6.7, p = 0.047 and 29.9 ± 3.5 vs 41.5 ± 3.9, p = 0.033). CsA treatment thus ameliorated cerebral reperfusion metabolism and infarct size. Cerebral microdialysis may be useful in evaluating putative neuroprotectants in ischaemic stroke.
Scaling and correlation properties of RR and QT intervals at the cellular level
Authors: Kim Jiyeong , Shah Disheet , Potapov Ilya , Latukka Joonas , Aalto-Setälä Katriina , Räsänen Esa 
Published: March 2019

AbstractWe study complex scaling properties of RR and QT intervals of electrocardiograms (ECGs) with their equivalences at the cellular level, that is, inter-beat intervals (IBI) and field potential durations (FPD) of spontaneously beating human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) aggregates. Our detrended fluctuation analysis and Poincaré plots reveal remarkable similarities between the ECG and hiPSC-CM data. In particular, no statistically significant difference was found in the short- and long-term scaling exponents α1 and α2 of RR and QT intervals and their cellular equivalences. Previously unknown scaling properties of FPDs of hiPSC-CM aggregates reveal that the increasing scaling exponent of QT intervals as a function of the time scale, is an intrinsic feature at the cellular level.
Differential role of prefrontal, temporal and parietal cortices in verbal and figural fluency: Implications for the supramodal contribution of executive functions
Authors: Ghanavati Elham , Salehinejad Mohammad Ali , Nejati Vahid , Nitsche Michael A. 
Published: March 2019

AbstractVerbal and figural fluency are related to executive functions (EFs), but the extent to which they benefit from executive resources and their respective cortical representations is not clear. Moreover, different brain areas and cognitive functions are involved in fluency processing. This study investigated effects of modulation of cortical excitability in the left dorsolateral prefrontal cortex (l-DLPFC), left temporal area and right posterior parietal cortex (r-PPC) with transcranial direct current stimulation (tDCS), on verbal and figural fluency. Fifteen healthy adult participants received anodal l-DLPFC (F3), anodal left temporal (T3), anodal r-PPC (P4) and sham tDCS (15 min, 1.5 mA). After five minutes of stimulation, participants underwent the verbal fluency (i.e., semantic and phonemic fluency tasks) and figural fluency tasks. Participants significantly generated more words with phonemic cues during anodal l-DLPFC tDCS and more words with semantic cues during both anodal left temporal and anodal l-DLPFC tDCS. In contrast, they generated more unique figures under anodal r-PPC and anodal l-DLPFC tDCS. Our results implicate that prefrontal regions and EFs are shared anatomical correlates and cognitive processes relevant for both, verbal and figural fluency (supramodal contribution of DLPFC activation), whereas r-PPC and left temporal cortex are more specifically involved in figural and semantic fluency (modality-specific contribution).
Transcriptome analysis of beta-lactamase genes in diarrheagenic Escherichia coli
Authors: Singh Taru , Singh Praveen Kumar , Das Shukla , Wani Sayim , Jawed Arshad , Dar Sajad Ahmad 
Published: March 2019

AbstractBeta (β)-lactamases are the most important agents that confer drug resistance among gram-negative bacteria. Continuous mutations in β-lactamases make them remarkably diverse. We carried out the transcriptome analysis of 10 β-lactamase genes of Extended-Spectrum β-lactamases (ESBL), Metallo β-lactamases (MBL), and AmpC β-lactamases (ABL) in drug-resistant and sensitive diarrheagenic E. coli (DEC) isolates obtained from children up to 5 years of age. Out of the 10 β-lactamase genes, four belonged to ESBL (TEM, SHV, CTX, and OXA); three to MBL (NDM-1, IMP, and VIM); and three to ABL (ACT, DHA and CMY) class of genes. The different categories of DEC were estimated for β-lactamases production using a set of conventional phenotypic tests, followed by detection of their messenger RNA (mRNA) expression. The study revealed a direct correlation between mRNA expression of these genes and the presence of antibiotic resistance; also corroborated by mutation analysis of the AmpC promoter region. All the 10 β-lactamase genes showed a significant increase in their expression levels in resistant isolates, compared to those of the sensitive isolates, indicating their possible role in the disease pathogenesis. Increase in mRNA expression of β-lactamase genes, and thereby virulence, may be due to multifactorial parameters causing phenotypic as well as genotypic changes. Our study highlights the necessity of instantaneous detection of β-lactamase gene expression to curb the overwhelming threat posed by emergence of drug resistance amongst the commensal E. coli strains in children from developing countries for larger public health interest.
Multi-drug use among patients with multiple sclerosis: A cross-sectional study of associations to clinicodemographic factors
Authors: Frahm Niklas , Hecker Michael , Zettl Uwe Klaus 
Published: March 2019

AbstractMultiple sclerosis (MS) is the most prevalent immune-mediated disease affecting the central nervous system. A treatment strategy with multiple therapies is a frequent clinical scenario. Unmonitored multi-drug use can lead to adverse outcomes, higher health care costs and medication non-adherence. The primary aim of this study was to evaluate the frequency of polypharmacy and related clinicodemographic factors in a single-center MS patient cohort. Furthermore, medication aspects of therapy management were examined. After the patients agreed to participate in the study, data were collected through patient interviews, patient records and clinical investigations. Subsequently, a statistical data analysis regarding various medication subgroups and polypharmacy (use of at least five drugs) was performed. Polypharmacy was observed in 56.5% of the patients (N = 306). High degrees of disability (odds ratio [OR] = 1.385), comorbidities (OR = 4.879) and inpatient treatment (OR = 5.146) were associated with a significantly higher risk of polypharmacy (p ≤ 0.001). Among patients with polypharmacy, disease-modifying drugs, antihypertensives, gastrointestinal drugs, thrombosis prophylactics, osteoporosis medications and sedatives were frequently used. In summary, polypharmacy plays a large role in MS patients, especially in those with higher degrees of disability, those with comorbidities and those treated in an inpatient setting.
Standard Audiograms for Koreans Derived through Hierarchical Clustering Using Data from the Korean National Health and Nutrition Examination Survey 2009–2012
Authors: Chang Young-Soo , Yoon Sung Hoon , Kim Jin Ryoul , Baek Sun-Young , Cho Young Sang , Hong Sung Hwa , Kim Seonwoo , Moon Il Joon 
Published: March 2019

AbstractAssessments of standardized region/population-specific audiological characteristics are needed for provision of effective rehabilitative services through reducing costs associated with hearing aids. This study aims to propose a set of standard audiograms representing the Korean population that were derived by analyzing data from the 2009–2012 Korea National Health and Nutrition Examination Survey (KNHANES), a nationwide epidemiologic study conducted by Korean government organizations. Standard audiograms were derived by applying a hierarchical clustering method from recorded audiologic data that were obtained independently at 6 frequencies for each ear: 0.5, 1.0, 2.0, 3.0, 4.0, and 6.0 kHz (in dB HL). To derive the optimal number of clusters of the desired standard audiograms, cubic clustering criterion, pseudo-F-, and pseudo-t2-statistics were calculated. These analyses resulted in 29 clusters representing a standard audiogram of the South Korean population. Eighteen of the clusters represented normal hearing audiograms (73.11%), while 11 represented hearing-impaired (HI) standard audiograms (27.89%). Of the 11 HI audiograms, 7 were defined as flat-type (17.81%), while the remaining 4 were defined as sloping-type (9.08%). In conclusion, 29 audiograms representing standard audiograms for the Korean population have been derived using KNHANES data. Improved understanding of the characteristics of each cluster may be helpful for development of more personalized, fixed-setting hearing aids.
Ultrafine particles and ozone perturb norepinephrine clearance rather than centrally generated sympathetic activity in humans
Authors: Heusser Karsten , Tank Jens , Holz Olaf , May Marcus , Brinkmann Julia , Engeli Stefan , Diedrich André , Framke Theodor , Koch Armin , Großhennig Anika , Jan Danser A. H. , Sweep Fred C. G. J. , Schindler Christoph , Schwarz Katharina , Krug Norbert , Jordan Jens , Hohlfeld Jens M. 
Published: March 2019

AbstractCardiovascular risk rapidly increased following exposure to air pollution. Changes in human autonomic regulation have been implicated based on epidemiological associations between exposure estimates and indirect autonomic nervous system measurements. We conducted a mechanistic study to test the hypothesis that, in healthy older individuals, well-defined experimental exposure to ultrafine carbon particles (UFP) increases sympathetic nervous system activity and more so with added ozone (O3). Eighteen participants (age >50 years, 6 women) were exposed to filtered air (Air), UFP, and UFP + O3 combination for 3 hours during intermittent bicycle ergometer training in a randomized, crossover, double-blind fashion. Two hours following exposure, respiration, electrocardiogram, blood pressure, and muscle sympathetic nerve activity (MSNA) were recorded at supine rest, during deep breathing, and during a Valsalva manoeuvre. Catechols and inflammatory marker levels were measured in venous blood samples. Induced sputum was obtained 3.5 h after exposure. Combined exposure to UFP + O3 but not UFP alone, caused a significant increase in sputum neutrophils and circulating leucocytes. Norepinephrine was modestly increased while the ratio between plasma dihydroxyphenylglycol (DHPG) and norepinephrine levels, a marker for norepinephrine clearance, was reduced with UFP + O3. Resting MSNA was not different (47 ± 12 with Air, 47 ± 14 with UFP, and 45 ± 14 bursts/min with UFP + O3). Indices of parasympathetic heart rate control were unaffected by experimental air pollution. Our study suggests that combined exposure to modest UFP and O3 levels increases peripheral norepinephrine availability through decreased clearance rather than changes in central autonomic activity. Pulmonary inflammatory response may have perturbed pulmonary endothelial norepinephrine clearance.
Detection of chromosome structural variation by targeted next-generation sequencing and a deep learning application
Authors: Park Hosub , Chun Sung-Min , Shim Jooyong , Oh Ji-Hye , Cho Eun Jeong , Hwang Hee Sang , Lee Ji-Young , Kim Deokhoon , Jang Se Jin , Nam Soo Jeong , Hwang Changha , Sohn Insuk , Sung Chang Ohk 
Published: March 2019

AbstractMolecular testing is increasingly important in cancer diagnosis. Targeted next generation sequencing (NGS) is widely accepted method but structural variation (SV) detection by targeted NGS remains challenging. In the brain tumor, identification of molecular alterations, including 1p/19q co-deletion, is essential for accurate glial tumor classification. Hence, we used targeted NGS to detect 1p/19q co-deletion using a newly developed deep learning (DL) model in 61 tumors, including 19 oligodendroglial tumors. An ensemble 1-dimentional convolution neural network was developed and used to detect the 1p/19q co-deletion. External validation was performed using 427 low-grade glial tumors from The Cancer Genome Atlas (TCGA). Manual review of the copy number plot from the targeted NGS identified the 1p/19q co-deletion in all 19 oligodendroglial tumors. Our DL model also perfectly detected the 1p/19q co-deletion (area under the curve, AUC = 1) in the testing set, and yielded reproducible results (AUC = 0.9652) in the validation set (n = 427), although the validation data were generated on a completely different platform (SNP Array 6.0 platform). In conclusion, targeted NGS using a cancer gene panel is a promising approach for classifying glial tumors, and DL can be successfully integrated for the SV detection in NGS data.
Ischaemic stroke in mice induces lung inflammation but not acute lung injury
Authors: Austin Victoria , Ku Jacqueline M. , Miller Alyson A , Vlahos Ross 
Published: March 2019

AbstractStroke is a major cause of death worldwide and ischemic stroke is the most common subtype accounting for approximately 80% of all cases. Pulmonary complications occur in the first few days to weeks following ischemic stroke and are a major contributor to morbidity and mortality. Acute lung injury (ALI) occurs in up to 30% of patients with subarachnoid haemorrhage but the incidence of ALI after ischemic stroke is unclear. As ischemic stroke is the most common subtype of stroke, it is important to understand the development of ALI following the initial ischemic injury to the brain. Therefore, this study investigated whether focal ischemic stroke causes lung inflammation and ALI in mice. Ischemic stroke caused a significant increase in bronchoalveolar lavage fluid (BALF) macrophages and neutrophils and whole lung tissue proinflammatory IL-1β mRNA expression but this did not translate into histologically evident ALI. Thus, it appears that lung inflammation, but not ALI, occurs after experimental ischemic stroke in mice. This has significant implications for organ donors as the lungs from patient’s dying of ischemic stroke are not severely damaged and could thus be used for transplantation in people awaiting this life-saving therapy.
“Prostate telocytes change their phenotype in response to castration or testosterone replacement”
Authors: Felisbino Sérgio Luis , Sanches Bruno Domingos Azevedo , Delella Flávia Karina , Scarano Wellerson Rodrigo , Dos Santos Fernanda Cristina Alcântara , Vilamaior Patrícia Simone Leite , Taboga Sebastião Roberto , Justulin Luis Antônio 
Published: March 2019

AbstractTelocytes are CD34-positive cells with a fusiform cell body and long, thin cytoplasmic projections called telopodes. These cells were detected in the stroma of various organs, including the prostate. The prostate is a complex gland capable of undergoing involution due to low testosterone levels; and this condition can be reversed with testosterone replacement. Telocyte function in the mature prostate remains to be dermined, and it is not known whether telocytes can take place in tissue remodeling during prostate involution and regrowth. The present study employed structural, ultrastructural and immunohistochemical methods to investigate the telocyte’s phenotypes in the ventral prostate (VP) from control (CT), castrated (CS) and testosterone replacement (TR) groups of adult male Wistar rats. Telocytes were found in the subepithelial, perimuscular and interstitical regions around glandular acini. Telocytes from CT animals have condensed chromatin and long and thin telopodes. In CS group, telocytes appeared quiescent and exhibited layers of folded up telopodes. After TR, telocytes presented loose chromatin, abundant rough endoplasmic reticulum and enlarged telopodes, closely associated with bundles of collagen fibrils. We called these cells “telocytes with a synthetic phenotype”. As testosterone levels and glandular morphology returned toward to the CT group parameters, after 10 days of TR, these telocytes progressively switched to the normal phenotype. Our results demonstrate that telocytes exhibit phenotypic plasticity upon androgen manipulation and interact with fibroblast and smooth muscle cells to maintain glandular architecture in control animals and during tissue remodeling after hormonal manipulation.