bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting nasopharyngeal carcinoma by artesunate through inhibiting Akt/mTOR and inducing oxidative stress
Authors: Li Qin , Ni Wei , Deng Zhifeng , Liu Minghe , She Lazhi , Xie Qiong 
Published: January 2017

AbstractDrug repurposing has become an alternative therapeutic strategy for cancer treatment given the known pharmacokinetics and toxicity. The inhibitory effects of artesunate have been reported in various cancers. In this work, we investigated the effects of artesunate in nasopharyngeal carcinoma (NPC). We demonstrate that artesunate significantly inhibits proliferation via arresting NPC cells at G2/M phase. It also induces apoptosis through caspase‐dependent and mitochondria‐independent pathways in multiple NPC cell lines. The combination of artesunate and cisplatin is synergistic in targeting NPC cells in in vitro cellular culture system and in vivo xenograft tumor models. Artesunate inhibits phosphorylation of essential molecules involved in Akt/mTOR pathway in NPC cells, such as Akt, mTOR, and 4EBP1, and its inhibitory effects are partially abolished by overexpression of constitutively active Akt. In addition, artesunate also induces mitochondrial dysfunction and oxidative stress via inhibiting mitochondrial respiration, increasing levels of mitochondrial superoxide and cellular reactive oxygen species (ROS), leading to decreased ATP levels. Two ROS scavengers partially abolish the inhibitory effects of artesunate in NPC cells. These data suggest that both inhibition of Akt/mTOR pathway and induction of ROS are required for the action of artesunate in NPC cells. Our work demonstrates that artesunate is a potential candidate for NPC treatment. Our work also highlights the critical roles of Akt/mTOR pathway and mitochondrial function in NPC cells.
Ethanol combined with heparin as a locking solution for the prevention of catheter related blood stream infections in hemodialysis patients: A prospective randomized study
Authors: Sofroniadou Sofia , Revela Ioanna , Kouloubinis Alexandros , Makriniotou Ioanna , Zerbala Sinodi , Smirloglou Despina , Kalocheretis Petros , Drouzas Apostolos , Samonis George , Iatrou Christos 
Published: January 2017

AbstractIntroduction: Ethanol lock solution has been mainly administered in paediatric and home parenteral nutrition patients in order to prevent catheter related blood stream infections (CRBSI). Its utility in hemodialysis (HD) patients with non‐tunneled‐uncuffed catheter (NTC) has been poorly explored.Methods: We conducted a prospective randomized study in chronic HD patients requiring a newly inserted NTC‐while awaiting for the maturation of an already established arteriovenous fistula (AVF) or arteriovenous graft (AVG) or tunneled‐cuffed catheter insertion. Patients were randomized in two groups: Group A, where the lock solution was ethanol 70% + unfractionated heparin 2000 U/mL and group B, that received only unfractionated heparin 2000 U/mL. Primary end point was CRBSIs whereas exit site infections, thrombotic and bleeding episodes were the secondary end points.Findings: One hundred three HD patients were enrolled in the study (group A, n = 52; group B, n = 51). The median number of catheter days was 32 for group A (range: 23–39) and 34 (range: 27–40) for group B with no statistically significant difference between the two groups. Group A (ethanol + heparin) demonstrated 4/52 episodes (7.69%) of CRBSI whereas Group B (heparin) 11/51 episodes (21.57%) (P = 0.04). CRBSI rates per 1000 catheter days were 2.53/1000 catheter days for group A and 6.7/1000 catheter days for group B (P = 0.04). Mean cumulative infection‐free catheter survival in the ethanol group did not differ significantly compared to the heparin group (log‐rank test = 2.99, P = 0.08). Thrombotic episodes did not differ between the two groups.Discussion: Locking of NTCs in HD patients with ethanol 70% + unfractionated heparin reduces CRBSI rates without increasing the thrombotic episodes.
Surface barrier layer effect in (In + Nb) co‐doped TiO2 ceramics: An alternative route to design low dielectric loss
Authors: Nachaithong Theeranuch , Kidkhunthod Pinit , Thongbai Prasit , Maensiri Santi 
Published: January 2017

AbstractGiant dielectric permittivity (ε′) with low loss tangent (tanδ) was reported in (In + Nb) co‐doped TiO2 ceramics. Either of electron‐pinned defect‐dipole or internal barrier layer capacitor model was proposed to be the origin of this high dielectric performance. Here, we proposed an effectively alternative route for designing low‐tanδ in co‐doped TiO2 ceramics by creating a resistive outer surface layer. A pure rutile‐TiO2 phase with a dense microstructure and homogeneous dispersion of dopants was achieved in (In + Nb) co‐doped TiO2 ceramics prepared by a simple sol‐gel method. Two giant dielectric responses were observed in low‐ and high‐frequency ranges, corresponding to extremely high ε′≈106‐107 and large ε′≈104‐105, respectively. After annealing in air, a low‐frequency dielectric response disappeared and could be restored by removing the outer surface of the annealed sample, indicating the dominant electrode effect in the initial sample. Annealing can cause improved dielectric properties with a temperature‐ and frequency‐independent ε′ value of ≈1.9 × 104 and cause a decrease in tanδ from 0.1 to 0.035. High dielectric performance in (In0.5Nb0.5)xTi1−xO2 ceramics can be achieved by eliminating the electrode effect and forming a resistive outer surface layer.
“Breastfeeding” without baby: A longitudinal, qualitative investigation of how mothers perceive, feel about, and practice human milk expression
Authors: Felice Julia P. , Geraghty Sheela R. , Quaglieri Caroline W. , Yamada Rei , Wong Adriana J. , Rasmussen Kathleen M. 
Published: January 2017

AbstractMost American mothers who produce human milk (HM) now pump in place of some or all feeding at the breast, and most American infants are now fed pumped HM. We aimed to investigate mothers' perceptions of, attitudes toward, and practices for pumping and providing pumped HM. Results related to pumping are reported here. We conducted in‐depth, semi‐structured interviews among a diverse sample of 20 mothers who pumped, following each from pregnancy through infant HM‐feeding cessation up to 1 year postpartum. Data were analyzed using thematic analysis with Atlas.ti. Mothers' reasons for pumping changed over time and reflected their needs and desires (e.g., latch difficulty, return to work, and increasing their milk supply). Mothers reported that pump type and quality were important to pumping success and that pumping was time‐consuming, costly, and unpleasant compared to feeding at the breast. Regardless of how often mothers pumped, most felt pumping was necessary to meet their infant HM‐feeding goals and was a welcome means of sharing with other caregivers the bonding opportunity and tasks they associated with feeding infants. Mothers interpreted output from pumping sessions to understand their ability to provide enough milk to meet their infants' needs. Mothers' reasons for pumping may signal constraints to infant HM feeding that may be addressed with policy changes. Mothers' attitudes and perceptions toward pumping indicate that, although pumping fills important and welcome roles for many mothers, the reality of its practice may make it an unacceptable or infeasible substitute for some.
Research of Adhesive Effect Enhanced by Pounding Brush on Second Lining Pounding Procedure for Japanese Scrolls
Authors: Oka Yasuhiro , Goto Akihiko 
Published: January 2017

Hanging scrolls are a traditional Japanese ornamental art, which allow paintings and calligraphy to be unrolled and hung on a wall or in an alcove for display, and rolled up and stored in a box. Hanging scrolls should hang straight when unrolled, and roll smoothly for proper storage, without damaging the artwork beneath. For this purpose, scrolls are lined with several layers of Japanese paper, and adhered together with a weak, aged paste made from wheat starch, which gives the paper the flexibility required when the scrolls are rolled up for storage. While this old paste facilitates winding a scroll because it does not become hard even when dried, it does not have sufficient adhesive effect to grip Japanese paper. In order to increase the adhesive power of this aged paste, craftsmen employ a traditional technique of pounding the paper with a special “pounding brush.”
This pounding technique is an important part of the fabrication process of hanging scrolls, but it is a difficult task for each generation to pass down the proper pounding technique. This study was intended to verify the effects of the pounding technique on aged paste and Japanese paper. We prepared samples with the pounding technique and investigated their adhesive properties of samples by peel text. In order to verify the importance of this traditional technique and the traditional materials, we compared and analyzed the differences in adhesion between craftsmen of different skill and differences introduced by paste concentration and backing paper quality.
Antimicrobial Activity of Ceftazidime-Avibactam against Gram-Negative Bacteria Isolated from Patients Hospitalized with Pneumonia in U.S. Medical Centers, 2011 to 2015
Authors: Sader Helio S. , Castanheira Mariana , Flamm Robert K. 
Published: January 2017

ABSTRACT

Bacterial isolates were collected from patients hospitalized with pneumonia (PHP), including ventilator-associated pneumonia (VAP), from 76 U.S. medical centers in 2011 to 2015. The Gram-negative organisms (
n
= 11,185, including 1,097 from VAP) were tested for susceptibility to ceftazidime-avibactam and comparators by the broth microdilution method. β-Lactamase-encoding genes were screened using a microarray-based assay on selected isolates.
Pseudomonas aeruginosa
and
Klebsiella
spp. were the most common Gram-negative bacteria isolated from PHP and VAP. Ceftazidime-avibactam was very active against
P. aeruginosa
(
n
= 3,402; MIC
50
/MIC
90
, 2 and 4 μg/ml; 96.6% susceptible), including isolates nonsusceptible to meropenem (86.3% susceptible to ceftazidime-avibactam), piperacillin-tazobactam (85.6% susceptible), or ceftazidime (80.6% susceptible). Ceftazidime-avibactam was also highly active against
Enterobacteriaceae
(MIC
50
/MIC
90
, 0.12 and 0.5 μg/ml; 99.9% susceptible), including carbapenem-resistant
Enterobacteriaceae
(CRE) (
n
= 189; MIC
50
/MIC
90
, 0.5 and 2 μg/ml; 98.0% susceptible) and multidrug-resistant (MDR) (
n
= 674; MIC
50
/MIC
90
, 0.25 and 1 μg/ml; 98.8% susceptible) and extensively drug-resistant (XDR) (
n
= 156; MIC
50
/MIC
90
, 0.5 and 2 μg/ml; 98.1% susceptible)
Enterobacteriaceae
isolates, as well as
Klebsiella
species isolates showing an extended-spectrum β-lactamase (ESBL) screening-positive phenotype (
n
= 433; MIC
50
/MIC
90
, 0.25 and 1 μg/ml; 99.5% susceptible). Among
Enterobacter
spp. (24.8% ceftazidime nonsusceptible), 99.8% of the isolates, including 99.4% of ceftazidime-nonsusceptible isolates, were susceptible to ceftazidime-avibactam. The most common β-lactamases detected among
Klebsiella pneumoniae
and
E. coli
isolates were
K. pneumoniae
carbapenemase (KPC)-like and CTX-M-15, respectively. Only 8 of 6,209
Enterobacteriaceae
isolates (0.1%) were ceftazidime-avibactam nonsusceptible, three NDM-1-producing strains with ceftazidime-avibactam MIC values of >32 μg/ml and five isolates with ceftazidime-avibactam MIC values of 16 μg/ml and negative results for all β-lactamases tested. Susceptibility rates among isolates from VAP were generally similar or slightly higher than those from all PHP.
MUC2 Mucin and Butyrate Contribute to the Synthesis of the Antimicrobial Peptide Cathelicidin in Response to Entamoeba histolytica- and Dextran Sodium Sulfate-Induced Colitis
Authors: Cobo Eduardo R. , Kissoon-Singh Vanessa , Moreau France , Holani Ravi , Chadee Kris 
Published: January 2017

ABSTRACTEmbedded in the colonic mucus are cathelicidins, small cationic peptides secreted by colonic epithelial cells. Humans and mice have one cathelicidin-related antimicrobial peptide (CRAMP) each, LL-37/hCAP-18 and Cramp, respectively, with related structure and functions. Altered production of MUC2 mucin and antimicrobial peptides is characteristic of intestinal amebiasis. The interactions between MUC2 mucin and cathelicidins in conferring innate immunity againstEntamoeba histolyticaare not well characterized. In this study, we quantified whether MUC2 expression and release could regulate the expression and secretion of cathelicidin LL-37 in colonic epithelial cells and in the colon. The synthesis of LL-37 was enhanced with butyrate (a product of bacterial fermentation) and interleukin-1β (IL-1β) (a proinflammatory cytokine in colitis) in the presence of exogenously added purified MUC2. The LL-37 responses to butyrate and IL-1β were higher in high-MUC2-producing cells than in lentivirus short hairpin RNA (shRNA) MUC2-silenced cells. Activation of cyclic adenylyl cyclase (AMP) and mitogen-activated protein kinase (MAPK) signaling pathways was necessary for the simultaneous expression of MUC2 and cathelicidins. In Muc2 mucin-deficient (Muc2−/−) mice, murine cathelicidin (Cramp) was significantly reduced compared to that inMuc2+/−andMuc2+/+littermates.E. histolytica-induced acute inflammation in colonic loops stimulated high levels of cathelicidin inMuc2+/+but not inMuc2−/−littermates. In dextran sodium sulfate (DSS)-induced colitis inMuc2+/+mice, which depletes the mucus barrier and goblet cell mucin,Crampexpression was significantly enhanced during restitution. These studies demonstrate regulatory mechanisms between MUC2 and cathelicidins in the colonic mucosa where an intact mucus barrier is essential for expression and secretion of cathelicidins in response toE. histolytica-and DSS-induced colitis.
Transcriptional Activation of Virulence Genes of Rhizobium etli
Authors: Wang Luyao , Lacroix Benoît , Guo Jianhua , Citovsky Vitaly 
Published: January 2017

ABSTRACT

Recently,
Rhizobium etli
, in addition to
Agrobacterium
spp., has emerged as a prokaryotic species whose genome encodes a functional machinery for DNA transfer to plant cells. To understand this
R. etli
-mediated genetic transformation, it would be useful to define how its
vir
genes respond to the host plants. Here, we explored the transcriptional activation of the
vir
genes contained on the
R. etli
p42a plasmid. Using a reporter construct harboring
lacZ
under the control of the
R. etli virE
promoter, we show that the signal phenolic molecule acetosyringone (AS) induces
R. etli vir
gene expression both in an
R. etli
background and in an
Agrobacterium tumefaciens
background. Furthermore, in both bacterial backgrounds, the p42a plasmid also promoted plant genetic transformation with a reporter transfer DNA (T-DNA). Importantly, the
R. etli vir
genes were transcriptionally activated by AS in a bacterial species-specific fashion in regard to the VirA/VirG signal sensor system, and this activation was induced by signals from the natural host species of this bacterium but not from nonhost plants. The early kinetics of transcriptional activation of the major
vir
genes of
R. etli
also revealed several features distinct from those known for
A. tumefaciens
: the expression of the
virG
gene reached saturation relatively quickly, and
virB2
, which in
R. etli
is located outside the
virB
operon, was expressed only at low levels and did not respond to AS. These differences in
vir
gene transcription may contribute to the lower efficiency of T-DNA transfer of
R. etli
p42a than of T-DNA transfer of pTiC58 of
A. tumefaciens
.

IMPORTANCE
The region encoding homologs of
Agrobacterium tumefaciens
virulence genes in the
Rhizobium etli
CE3 p42a plasmid was the first endogenous virulence system encoded by the genome of a non-
Agrobacterium
species demonstrated to be functional in DNA transfer and stable integration into the plant cell genome. In this study, we explored the transcriptional regulation and induction of virulence genes in
R. etli
and show similarities to and differences from those of their
A. tumefaciens
counterparts, contributing to an understanding and a comparison of these two systems. Whereas most
vir
genes in
R. etli
follow an induction pattern similar to that of
A. tumefaciens vir
genes, a few significant differences may at least in part explain the variations in T-DNA transfer efficiency.
Detection of Antigenic Variants of Subtype H3 Swine Influenza A Viruses from Clinical Samples
Authors: Martin Brigitte E. , Bowman Andrew S. , Li Lei , Nolting Jacqueline M. , Smith David R. , Hanson Larry A. , Wan Xiu-Feng 
Published: January 2017

ABSTRACT
A large population of genetically and antigenically diverse influenza A viruses (IAVs) are circulating among the swine population, playing an important role in influenza ecology. Swine IAVs not only cause outbreaks among swine but also can be transmitted to humans, causing sporadic infections and even pandemic outbreaks. Antigenic characterizations of swine IAVs are key to understanding the natural history of these viruses in swine and to selecting strains for effective vaccines. However, influenza outbreaks generally spread rapidly among swine, and the conventional methods for antigenic characterization require virus propagation, a time-consuming process that can significantly reduce the effectiveness of vaccination programs. We developed and validated a rapid, sensitive, and robust method, the polyclonal serum-based proximity ligation assay (polyPLA), to identify antigenic variants of subtype H3N2 swine IAVs. This method utilizes oligonucleotide-conjugated polyclonal antibodies and quantifies antibody-antigen binding affinities by quantitative reverse transcription-PCR (RT-PCR). Results showed the assay can rapidly detect H3N2 IAVs directly from nasal wash or nasal swab samples collected from laboratory-challenged animals or during influenza surveillance at county fairs. In addition, polyPLA can accurately separate the viruses at two contemporary swine IAV antigenic clusters (H3N2 swine IAV-α and H3N2 swine IAV-ß) with a sensitivity of 84.9% and a specificity of 100.0%. The polyPLA can be routinely used in surveillance programs to detect antigenic variants of influenza viruses and to select vaccine strains for use in controlling and preventing disease in swine.
BRD4 Couples NF-κB/RelA with Airway Inflammation and the IRF-RIG-I Amplification Loop in Respiratory Syncytial Virus Infection
Authors: Tian Bing , Yang Jun , Zhao Yingxin , Ivanciuc Teodora , Sun Hong , Garofalo Roberto P. , Brasier Allan R. 
Published: January 2017

ABSTRACT

The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to respiratory syncytial virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NF-κB/RelA. BRD4 is functionally required for expression of the NF-κB-dependent inflammatory gene regulatory network (GRN), including the IFN response factor 1 (IRF1) and IRF7, which mediate a cross talk pathway for RIG-I upregulation. Mechanistically, BRD4 is required for cyclin-dependent kinase 9 (CDK9) recruitment and phospho-Ser 2 carboxy-terminal domain (CTD) RNA polymerase (Pol) II formation on the promoters of
IRF1
,
IRF7
, and
RIG-I
, producing their enhanced expression by transcriptional elongation. We also find that BRD4 independently regulates CDK9/phospho-Ser 2 CTD RNA Pol II recruitment to the IRF3-dependent IFN-stimulated genes (ISGs).
In vivo
, poly(I·C)-induced neutrophilia and mucosal chemokine production are blocked by a small-molecule BRD4 bromodomain inhibitor. Similarly, BRD4 inhibition reduces RSV-induced neutrophilia, mucosal CXC chemokine expression, activation of the IRF7-RIG-I autoamplification loop, mucosal IFN expression, and airway obstruction. RSV infection activates BRD4 acetyltransferase activity on histone H3 Lys (K) 122, demonstrating that RSV infection activates BRD4
in vivo
. These data validate BRD4 as a major effector of RSV-induced inflammation and disease. BRD4 is required for coupling NF-κB to expression of inflammatory genes and the IRF-RIG-I autoamplification pathway and independently facilitates antiviral ISG expression. BRD4 inhibition may be a strategy to reduce exuberant virus-induced mucosal airway inflammation.

IMPORTANCE
In the United States, 2.1 million children annually require medical attention for RSV infections. A first line of defense is the expression of the innate gene network by infected epithelial cells. Expression of the innate response requires the recruitment of transcriptional elongation factors to rapidly induce innate response genes through an unknown mechanism. We discovered that RSV infection induces a complex of bromodomain containing 4 (BRD4) with NF-κB and cyclin-dependent kinase 9 (CDK9). BRD4 is required for stable CDK9 binding, phospho-Ser 2 RNA Pol II formation, and histone acetyltransferase activity. Inhibition of BRD4 blocks Toll-like receptor 3 (TLR3)-dependent neutrophilia and RSV-induced inflammation, demonstrating its importance in the mucosal innate response
in vivo
. Our study shows that BRD4 plays a central role in inflammation and activation of the IRF7-RIG-I amplification loop vital for mucosal interferon expression. BRD4 inhibition may be a strategy for modulating exuberant mucosal airway inflammation.