bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Genes
degQ
,
pps
, and
lpa-8
(
sfp
) Are Responsible for Conversion of
Bacillus subtilis
168 to Plipastatin Production
Authors: Tsuge Kenji , Ano Takashi , Hirai Mitsuyo , Nakamura Yoshiyuki , Shoda Makoto 
Published: October 2018

ABSTRACT

Bacillus subtilis
YB8 produces the lipopeptide antibiotic plipastatin.
B. subtilis
MI113, which is a derivative of strain 168, was converted into a new plipastatin producer, strain 406, by competence transformation with the chromosomal DNA of YB8. Transposon mini-Tn
10
insertional mutagenesis was applied to strain 406, which revealed that
lpa-8
(
sfp
) (encoding 4′-phosphopantetheinyl transferase) and the
pps
operon (located between 167 and 171°) are essential for plipastatin production. The
pps
operon was previously suggested to encode putative peptide synthetases (A. Tognoni, E. Franchi, C. Magistrelli, E. Colombo, P. Cosmina, and G. Grandi, Microbiology 141:645–648, 1995) and was thought to be the fengycin operon (V. Tosato, A. M. Albertini, M. Zotti, S. Sonda, and C. V. Bruschi, Microbiology 143:3443–3450, 1997). We claim that the
pps
operon is the
pli
operon, encoding plipastatin synthetase. By using a new high-performance liquid chromatography system, we revealed that strain 168 expressing only
lpa-8
can also produce plipastatin, although the yield is very low. However, the introduction of the pleiotropic regulator
degQ
of strain YB8 into strain 168 expressing
lpa-8
resulted in a 10-fold increase in the production of plipastatin.
Apraxia screening predicts Alzheimer pathology in frontotemporal dementia
Authors: Pawlowski Matthias , Joksch Viktoria , Wiendl Heinz , Meuth Sven G , Duning Thomas , Johnen Andreas 
Published: October 2018

ObjectivesFrontotemporal dementia (FTD) is a heterogeneous clinical syndrome linked to diverse types of underlying neuropathology. Diagnosis is mainly based on clinical presentation and accurate prediction of underlying neuropathology remains difficult.MethodsWe present a large cohort of patients with FTD spectrum diseases (n=84). All patients were thoroughly characterised by cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers, neuroimaging, neuropsychological testing and standardised apraxia screening.ResultsA potential AD pathology was found in 43% of patients with FTD. CSF AD biomarker levels positively correlated with AD-typical apraxia scores in patients with FTD. The discriminative power of apraxia test results indicative of AD pathology was high (sensitivity: 90%, specificity: 66%).ConclusionsApraxia is common in neurodegenerative dementias but under-represented in clinical workup and diagnostic criteria. Standardised apraxia screening may serve as bedside test to objectify an AD-typical apraxia profile as an early and robust sign of AD pathology in patients with FTD.
Gaps in the evidence for treatment decisions in cystic fibrosis: a systematic review
Authors: Rowbotham Nicola Jane , Smith Sherie , Prayle Andrew P , Robinson Karen A , Smyth Alan Robert 
Published: October 2018

IntroductionCystic fibrosis (CF) is a multisystem disorder. Treatment is complex and evidence for treatment decisions may be absent. Characterising gaps in the research evidence will highlight treatment uncertainties and help prioritise research questions. We systematically identified the evidence gaps for treatment decisions in CF.MethodsWe searched for systematic reviews and guidelines on treatment interventions in CF. Two researchers identified eligible reviews with arbitration from a third. Using a structured framework, we extracted and characterised evidence gaps.ResultsThere were 73 reviews and 21 guidelines that met our inclusion criteria. From these, we identified 148 evidence gaps across a range of treatment areas. We found 111 evidence gaps through systematic reviews and a further 37 from guidelines. The reason for an evidence gap could only be reliably characterised for systematic reviews. In most cases, there was more than one explanation—most commonly few or no trials (97/111 evidence gaps). Other important factors leading to evidence gaps were small sample size (49/111), inadequate duration of follow-up (38/111) or intervention (37/111) and factors relating to outcomes (35/111). Evidence gaps from both systematic reviews and guidelines fell into the following categories: Respiratory (91); Gastrointestinal (20); PhysiotherapyandExercise (16); Musculoskeletal (6); Endocrine (4); Basic defect of CF (8); Psychosocial (2); Ears, Nose and Throat (1).ConclusionsWe have compiled an up-to-date list of treatment uncertainties in CF and the reasons for these uncertainties. These can be used as a resource to aid researchers and funders when planning future trials.PROSPERO registration numberPre-results; CRD42015030111.
Revolution or redux? Assessing IQOS through a precursor product
Authors: Elias Jesse , Dutra Lauren M , St. Helen Gideon , Ling Pamela M 
Published: October 2018

BackgroundPhilip Morris International (PMI) currently claims that its heated tobacco product, IQOS, reduces health risk by reducing users’ exposure to harmful and potentially harmful constituents present in tobacco smoke. Given the tobacco industry’s long history of misrepresenting and obfuscating research, independent assessment of PMI’s claims is important. Analysis of Accord, a failed but strikingly similar precursor to IQOS, may help contextualise PMI’s claims in its Modified Risk Tobacco Product (MRTP) application.MethodsWe analysed previously secret internal Philip Morris (PM) and PMI documents, public communications and MRTP application.ResultsPM marketed Accord as a ‘cleaner’ tobacco product in an attempt to address smokers’ growing health concerns without making explicit health claims. While PM communications asserted that Accord reduced users’ exposure to harmful constituents, company scientists and executives consistently stressed to both regulators and the public that such reductions did not render Accord safer. IQOS’s design and marketing are similar to Accord’s. On the basis of aerosol chemistry data, IQOS reduces user exposure to some compounds compared with Accord but raises them for others.DiscussionIQOS appears to be a variant of Accord without consistent improvements in exposure to aerosol toxic compounds. In contrast to PM’s past claims for Accord, PMI now claims in its MRTP application that IQOS reduces health risk. This shift in stance is likely not the result of any toxicological difference between Accord and IQOS, but rather a change in the social and regulatory landscape permitting these claims.
The optimization of electrospray process based on auxiliary electrode
Authors: Liu Y. F. , Zhang Y. , Dai T. T. , Lei T. P. 
Published: October 2018

In order to control the charged jet and deposition area of the glass frit in the electrostatic spray system, the nozzles with/without sleeve-type auxiliary electrode are comparatively studied through simulations and experiments. The influence of the voltage applied on the auxiliary electrode and its diameter is analyzed. According to the vector diagram and the distribution of electric field intensity, the optimal values for the applied voltage and the diameter of the auxiliary electrode are determined for the present work, i.e. 1.5 kV and 6 mm, respectively. The experimental results further demonstrate the nozzle with the auxiliary electrode is much better than the one without the electrode, and under the above optimized condition the charged jet can be well controlled to deposit glass frit film on silicon wafer with a line width of 330 μm, which is much more narrow than the conventional nozzle (without the electrode). This work will offer another good way for better control of the deposition during electrostatic spray process.
WARMING AND INCOME GROWTH IN THE UNITED STATES: A HETEROGENEOUS, COMMON FACTOR DYNAMIC PANEL ANALYSIS
Authors: LIDDLE BRANTLEY 
Published: October 2018

This paper analyzes whether temperature changes influence economic growth in the contiguous 48 US states by employing panel methods that address both heterogeneity and cross-sectional dependence. Ultimately, it is determined that the negative effect of warming (initially proxied by cooling degree days) is restricted to agriculture GDP. But when weathers’ impact was measured by average summer temperature, the negative effect — still mostly restricted to agriculture GDP — was substantially and significantly larger (a finding similar to previous work) and geographically uniform. Yet, the model’s dynamics suggested that the magnitude of the short-run impact was larger (in absolute terms) than the long-run impact.
LPA4-Mediated Vascular Network Formation Increases the Efficacy of Anti–PD-1 Therapy against Brain Tumors
Authors: Eino Daisuke , Tsukada Yohei , Naito Hisamichi , Kanemura Yonehiro , Iba Tomohiro , Wakabayashi Taku , Muramatsu Fumitaka , Kidoya Hiroyasu , Arita Hideyuki , Kagawa Naoki , Fujimoto Yasunori , Takara Kazuhiro , Kishima Haruhiko , Takakura Nobuyuki 
Published: October 2018

Abstract

The structure and function of tumor blood vessels profoundly affects the tumor microenvironment. Signals mediated through the lysophosphatidic acid receptor 4 (LPA4) promote vascular network formation to restore normal vascular barrier function in subcutaneous tumors and thus improve drug delivery. However, the characteristics of the vasculature vary by organ and tumor types, and how drug delivery and leukocyte trafficking are affected by modification of vascular function by LPA in different cancers is unclear. Here, we show that LPA4 activation promotes the formation of fine vascular structures in brain tumors. RhoA/ROCK signaling contributed to LPA-induced endothelial cell–cell adhesion, and RhoA/ROCK activity following LPA4 stimulation regulated expression of VCAM-1. This resulted in increased lymphocyte infiltration into the tumor. LPA improved delivery of exogenous IgG into brain tumors and enhanced the anticancer effect of anti–programmed cell death-1 antibody therapy. These results indicate the effects of LPA on vascular structure and function apply not only to chemotherapy but also to immunotherapy.

Significance:
These findings demonstrate that lysophosphatidic acid, a lipid mediator, promotes development of a fine capillary network in brain tumors by inducing tightening of endothelial cell-to-cell adhesion, facilitating improved drug delivery, and lymphocyte penetration.
PRMT5 Circular RNA Promotes Metastasis of Urothelial Carcinoma of the Bladder through Sponging miR-30c to Induce Epithelial–Mesenchymal Transition
Authors: Chen Xin , Chen Ri-Xin , Wei Wen-Su , Li Yong-Hong , Feng Zi-Hao , Tan Lei , Chen Jie-Wei , Yuan Gang-Jun , Chen Si-Liang , Guo Sheng-Jie , Xiao Kang-Hua , Liu Zhuo-Wei , Luo Jun-Hang , Zhou Fang-Jian , Xie Dan 
Published: October 2018

Abstract
Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs.
Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin, in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA).
Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis.
Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot
Authors: Dubes Virginie , Benoist David , Roubertie François , Gilbert Stephen H. , Constantin Marion , Charron Sabine , Elbes Delphine , Vieillot Delphine , Quesson Bruno , Cochet Hubert , Haïssaguerre Michel , Rooryck Caroline , Bordachar Pierre , Thambo Jean-Benoit , Bernus Olivier 
Published: October 2018

Background:
Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae.

Methods:
Piglets underwent a tetralogy of Fallot repair–like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot.

Results:
Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols.

Conclusions:
We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.
Common Coding Variants in
SCN10A
Are Associated With the Nav1.8 Late Current and Cardiac Conduction
Authors: Macri Vincenzo , Brody Jennifer A. , Arking Dan E. , Hucker William J. , Yin Xiaoyan , Lin Honghuang , Mills Robert W. , Sinner Moritz F. , Lubitz Steven A. , Liu Ching-Ti , Morrison Alanna C. , Alonso Alvaro , Li Ning , Fedorov Vadim V. , Janssen Paul M. , Bis Joshua C. , Heckbert Susan R. , Dolmatova Elena V. , Lumley Thomas , Sitlani Colleen M. , Cupples L. Adrienne , Pulit Sara L. , Newton-Cheh Christopher , Barnard John , Smith Jonathan D. , Van Wagoner David R. , Chung Mina K. , Vlahakes Gus J. , O’Donnell Christopher J. , Rotter Jerome I. , Margulies Kenneth B. , Morley Michael P. , Cappola Thomas P. , Benjamin Emelia J. , Muzny Donna , Gibbs Richard A. , Jackson Rebecca D. , Magnani Jared W. , Herndon Caroline N. , Rich Stephen S. , Psaty Bruce M. , Milan David J. , Boerwinkle Eric , Mohler Peter J. , Sotoodehnia Nona , Ellinor Patrick T. ,   Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Sequencing Project, NHLBI Exome Sequencing Project†
Published: October 2018

Background:

Genetic variants at the
SCN5A
/
SCN10A
locus are strongly associated with electrocardiographic PR and QRS intervals. While
SCN5A
is the canonical cardiac sodium channel gene, the role of
SCN10A
in cardiac conduction is less well characterized.

Methods:

We sequenced the
SCN10A
locus in 3699 European-ancestry individuals to identify variants associated with cardiac conduction, and replicated our findings in 21,000 individuals of European ancestry. We examined association with expression in human atrial tissue. We explored the biophysical effect of variation on channel function using cellular electrophysiology.

Results:

We identified 2 intronic single nucleotide polymorphisms in high linkage disequilibrium (
r

2
=0.86) with each other to be the strongest signals for PR (rs10428132, β=−4.74,
P
=1.52×10
−14
) and QRS intervals (rs6599251, QRS β=−0.73;
P
=1.2×10
−4
), respectively. Although these variants were not associated with
SCN5A
or
SCN10A
expression in human atrial tissue (n=490), they were in high linkage disequilibrium (
r

2
≥0.72) with a common
SCN10A
missense variant, rs6795970 (V1073A). In total, we identified 7 missense variants, 4 of which (I962V, P1045T, V1073A, and L1092P) were associated with cardiac conduction. These 4 missense variants cluster in the cytoplasmic linker of the second and third domains of the SCN10A protein and together form 6 common haplotypes. Using cellular electrophysiology, we found that haplotypes associated with shorter PR intervals had a significantly larger percentage of late current compared with wild-type (I962V+V1073A+L1092P, 20.2±3.3%,
P
=0.03, and I962V+V1073A, 22.4±0.8%,
P
=0.0004 versus wild-type 11.7±1.6%), and the haplotype associated with the longest PR interval had a significantly smaller late current percentage (P1045T, 6.4±1.2%,
P
=0.03).

Conclusions:

Our findings suggest an association between genetic variation in
SCN10A
, the late sodium current, and alterations in cardiac conduction.
Improving Interpretation of Cardiac Phenotypes and Enhancing Discovery With Expanded Knowledge in the Gene Ontology
Authors: Lovering Ruth C. , Roncaglia Paola , Howe Douglas G. , Laulederkind Stanley J.F. , Khodiyar Varsha K. , Berardini Tanya Z. , Tweedie Susan , Foulger Rebecca E. , Osumi-Sutherland David , Campbell Nancy H. , Huntley Rachael P. , Talmud Philippa J. , Blake Judith A. , Breckenridge Ross , Riley Paul R. , Lambiase Pier D. , Elliott Perry M. , Clapp Lucie , Tinker Andrew , Hill David P. 
Published: October 2018

Background:
A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products.

Methods and Results:
In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci.

Conclusions:
We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects.
GEÇİCİ GÖÇMENLİKTEN YERLEŞİKLİĞE : YÜKSEKÖĞRETİM GENÇLİĞİNİN GELECEKTEKİ GÖÇ POTANSİYELLERİ
Authors: ESGİN GÜNDER Esma 
Published: October 2018

Toplumun yeniden yapılandırılması açısından göç olgusu
önemli bir role sahiptir. Göç, ekonomik, sosyal, kültürel ve politik bazı
değişikliklere yol açabileceği gibi aynı zamanda bu tür değişiklerden de
kaynaklanabilmektedir. Bu nedenle göç olgusu, temelinde yatan nedenleri ve
sonuçlarıyla birlikte sosyo-kültürel bir değişim aracı olarak
değerlendirilebilir. Günümüzde özellikle küreselleşme çerçevesinde bireylerin
gerek ulusal gerekse uluslararası hareketliliği bilişim teknolojileri
aracılığıyla bilginin akışıyla birlikte ele alınmaktadır.

Bu çalışmada göç ve eğitim ilişkisi bağlamında,
üniversite eğitimi alma amacıyla yaşadıkları şehirlerden öğrenim gördükleri
şehre “geçici” göç eden yükseköğretim öğrencilerinin göçe yönelik algıları ve
gelecekteki göç potansiyelleri irdelenmiştir. Bu amaçla çalışmada
nitel araştırma desenlerinden “olgu
bilim (fenomenoloji) deseni” kullanılmıştır. Çalışma grubunu, 2017-2018
öğretim yılı bahar döneminde Manisa Celal Bayar Üniversitesi Salihli M.Y.O. Çocuk Gelişimi Programı'nda öğrenim
gören otuz iki son sınıf öğrencisi oluşturmaktadır. Elde edilen bulgular
yükseköğretim gençliğinin gündelik hayatı değiştirme ve öğrenim görme amacıyla
gerçekleştirdiği geçici göç hareketliliğinin istihdam amacıyla da süreklilik
göstereceği yönündedir.
Mobilizing the “State Papers” of Empire: John Bruce, Early Modernity, and the Bureaucratic Archives of Britain
Authors: Siddique Asheesh Kapur 
Published: October 2018

Abstract
This article examines John Bruce’s vision of the bureaucratic archives of the British state and empire at the end of the eighteenth century. As Historiographer to the East India Company and Keeper of State Papers in the 1790s and early 1800s, Bruce used the archives of corporate and state government as sources of bureaucratic knowledge to justify and plan imperial and domestic policy. In this way, Bruce deployed a strategy of governance by the authority of “state papers,” rooted in early modern political practice, across imperial and domestic government. The demise of Bruce’s influence signaled the waning of this role of the archive as a technology of governance in Britain during the nineteenth century.
Reflections on the Critical Edition of the Hebrew Text of Ben Sira. Between Eclecticism and Pragmatism
Authors: Rey Jean-Sébastien 
Published: October 2018

AbstractThis article aims to confront and question the theoretical distinction between textual criticism and redaction criticism from a pragmatic perspective. In order to accomplish this goal, we will examine the Hebrew manuscripts of Ben Sira as a test case and a paradigmatic example. The following situations will be examined: cases of irreducible divergences between the Hebrew witnesses, scribal “mistakes,” doublets in MSS A and B, and the so-called Hebrew II.
Intraseasonal Variability in a Cloud-Permitting Near-Global Equatorial Aquaplanet Model
Authors: Khairoutdinov Marat F. , Emanuel Kerry 
Published: October 2018

Abstract
Recent studies have suggested that the Madden–Julian oscillation is a result of an instability driven mainly by cloud–radiation feedbacks, similar in character to self-aggregation of convection in nonrotating, cloud-permitting simulations of radiative–convective equilibrium (RCE). Here we bolster that inference by simulating radiative–convective equilibrium states on a rotating sphere with constant sea surface temperature, using the cloud-permitting System for Atmospheric Modeling (SAM) with 20-km grid spacing and extending to walls at 46° latitude in each hemisphere. Mechanism-denial experiments reveal that cloud–radiation interaction is the quintessential driving mechanism of the simulated MJO-like disturbances, but wind-induced surface heat exchange (WISHE) feedbacks are the primary driver of its eastward propagation. WISHE may also explain the faster Kelvin-like modes in the simulations. These conclusions are supported by a linear stability analysis of RCE states on an equatorial beta plane.