bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal Structure of the Extended-Spectrum β-Lactamase PER-2 and Insights into the Role of Specific Residues in the Interaction with β-Lactams and β-Lactamase Inhibitors
Authors: Ruggiero Melina , Kerff Frédéric , Herman Raphaël , Sapunaric Frédéric , Galleni Moreno , Gutkind Gabriel , Charlier Paulette , Sauvage Eric , Power Pablo 
Published: July 2014

ABSTRACT

PER-2 belongs to a small (7 members to date) group of extended-spectrum β-lactamases. It has 88% amino acid identity with PER-1 and both display high catalytic efficiencies toward most β-lactams. In this study, we determined the X-ray structure of PER-2 at 2.20 Å and evaluated the possible role of several residues in the structure and activity toward β-lactams and mechanism-based inhibitors. PER-2 is defined by the presence of a singular
trans
bond between residues 166 to 167, which generates an inverted Ω loop, an expanded fold of this domain that results in a wide active site cavity that allows for efficient hydrolysis of antibiotics like the oxyimino-cephalosporins, and a series of exclusive interactions between residues not frequently involved in the stabilization of the active site in other class A β-lactamases. PER β-lactamases might be included within a cluster of evolutionarily related enzymes harboring the conserved residues Asp136 and Asn179. Other signature residues that define these enzymes seem to be Gln69, Arg220, Thr237, and probably Arg/Lys240A (“A” indicates an insertion according to Ambler's scheme for residue numbering in PER β-lactamases), with structurally important roles in the stabilization of the active site and proper orientation of catalytic water molecules, among others. We propose, supported by simulated models of PER-2 in combination with different β-lactams, the presence of a hydrogen-bond network connecting Ser70-Gln69-water-Thr237-Arg220 that might be important for the proper activity and inhibition of the enzyme. Therefore, we expect that mutations occurring in these positions will have impacts on the overall hydrolytic behavior.
Double Mutation in the
pfmdr1
Gene Is Associated with Emergence of Chloroquine-Resistant Plasmodium falciparum Malaria in Eastern India
Authors: Das Sabyasachi , Mahapatra Santanu Kar , Tripathy Satyajit , Chattopadhyay Sourav , Dash Sandeep Kumar , Mandal Debasis , Das Balaram , Hati Amiya Kumar , Roy Somenath 
Published: July 2014

ABSTRACT

Malaria is a major public health problem in tropical and subtropical countries, including India. This study elucidates the cause of chloroquine treatment failure (for
Plasmodium falciparum
infection) before the introduction of artemisinin combination therapy. One hundred twenty-six patients were randomized to chloroquine treatment, and the therapeutic efficacy was monitored from days 1 to 28. An
in vitro
susceptibility test was performed with all isolates. Parasitic DNA was isolated, followed by PCR and restriction digestion of different codons of the
pfcrt
gene (codons 72 to 76) and the
pfmdr1
gene (N86Y, Y184F, S1034C, N1042D, and D1246Y). Finally, sequencing was done to confirm the mutations. Forty-three (34.13%) early treatment failure cases and 16 (12.69%) late treatment failure cases were observed after chloroquine treatment.
In vitro
chloroquine resistance was found in 103 isolates (81.75%). Twenty-six (60.47%) early treatment failure cases and 6 (37.5%) late treatment failure cases were associated with the CVMNK-

Y

YSN

Y

allele (the underlined amino acids are those that were mutated). Moreover, the CV

IE

K-

Y

YSN

Y

allele was found in 8 early treatment failure (18.60%) and 2 late treatment failure (12.5%) cases. The presence of the wild-type
pfcrt
(CVMNK) and
pfmdr1
(

Y

YSN

Y

) double mutant allele in chloroquine-nonresponsive cases was quite uncommon.
In vivo
chloroquine treatment failure and
in vitro
chloroquine resistance were strongly correlated with the CVMNK-

Y

YSN

Y

and CV

IE

K-

Y

YSN

Y

haplotypes (
P
< 0.01).
In Vivo
Study of the Efficacy of the Aromatic Water of Zataria multiflora on Hydatid Cysts
Authors: Moazeni Mohammad , Larki Sara , Saharkhiz Mohammad Jamal , Oryan Ahmad , Ansary Lari Maryam , Mootabi Alavi Amir 
Published: July 2014

ABSTRACT

Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) were employed to determine the chemical composition of the essential oil (EO) from aromatic water (AW) of
Zataria multiflora
. Thymol (66.9%), carvacrol (15.2%), and carvone (7.3%) were found to be the major EO constituents. Eighty laboratory BALB/c mice were infected intraperitoneally by injection of 1,500 viable protoscolices and were divided into prevention (40 mice) and therapeutic (40 mice) groups. To prove the preventive effect of the
Z. multiflora
AW on development of hydatid cysts, the 40 infected mice were allocated into three treatment groups, including the albendazole group (10 mice that received 150 mg/kg body weight/day for 10 days), the
Z. multiflora
AW group (15 mice that received 20 ml/liter in drinking water for 8 months), and a control group (15 mice that received no treatment). To estimate the therapeutic effect of the
Z. multiflora
AW on the hydatid cyst, after 8 months of infection, the 15 remaining mice were allocated into three experimental treatment groups of five animals each, including the albendazole group (300 mg/kg/day for 20 days),
Z. multiflora
AW group (40 ml/liter in drinking water for 30 days), and control group (no treatment). All mice were then euthanized, and the sizes and weights of the cysts as well as their ultrastructural changes were investigated. The weights and sizes of the hydatid cysts significantly decreased upon treatment with the
Z. multiflora
AW in both the preventive and therapeutic groups (
P
< 0.05). The results of scanning electron microscopy also showed considerable damage in the germinal layer of the hydatid cysts recovered from the treated animals.
Efficacy of PTX3 and Posaconazole Combination in a Rat Model of Invasive Pulmonary Aspergillosis
Authors: Marra Emanuele , Sousa Vitor L. , Gaziano Roberta , Pacello M. Lucrezia , Arseni Brunilde , Aurisicchio Luigi , De Santis Rita , Salvatori Giovanni 
Published: July 2014

ABSTRACT
Posaconazole is currently used for the prophylaxis of invasive pulmonary aspergillosis (IPA). Limitations to posaconazole usage are drug-drug interactions and side effects. PTX3 is an innate immunity glycoprotein with opsonic activity, proven to be protective in IPA animal models. This study investigated the combination of posaconazole with PTX3. The results indicate synergy between PTX3 and posaconazole against aspergillosis, suggesting that a combination of reduced doses of posaconazole with the immune response enhancer PTX3 might represent a treatment option with a higher therapeutic index than posaconazole.
Tn
5253
Family Integrative and Conjugative Elements Carrying
mef
(I) and
catQ
Determinants in Streptococcus pneumoniae and Streptococcus pyogenes
Authors: Mingoia Marina , Morici Eleonora , Morroni Gianluca , Giovanetti Eleonora , Del Grosso Maria , Pantosti Annalisa , Varaldo Pietro E. 
Published: July 2014

ABSTRACT

The linkage between the macrolide efflux gene
mef
(I) and the chloramphenicol inactivation gene
catQ
was first described in
Streptococcus pneumoniae
(strain Spn529), where the two genes are located in a module designated IQ element. Subsequently, two different defective IQ elements were detected in
Streptococcus pyogenes
(strains Spy029 and Spy005). The genetic elements carrying the three IQ elements were characterized, and all were found to be Tn
5253
family integrative and conjugative elements (ICEs). The ICE from
S. pneumoniae
(ICE
Spn
529IQ) was sequenced, whereas the ICEs from
S. pyogenes
(ICE
Spy
029IQ and ICE
Spy
005IQ, the first Tn
5253
-like ICEs reported in this species) were characterized by PCR mapping, partial sequencing, and restriction analysis. ICE
Spn
529IQ and ICE
Spy
029IQ were found to share the

int
Sp

23FST81
integrase gene and an identical Tn
916
fragment, whereas ICE
Spy
005IQ has

int
5252

and lacks Tn
916
. All three ICEs were found to lack the linearized pC194 plasmid that is usually associated with Tn
5253
-like ICEs, and all displayed a single copy of a toxin-antitoxin operon that is typically contained in the direct repeats flanking the excisable pC194 region when this region is present. Two different insertion sites of the IQ elements were detected, one in ICE
Spn
529IQ and ICE
Spy
029IQ, and another in ICE
Spy
005IQ. The chromosomal integration of the three ICEs was site specific, depending on the integrase (

int
Sp

23FST81
or

int
5252

). Only ICE
Spy
005IQ was excised in circular form and transferred by conjugation. By transformation,
mef
(I) and
catQ
were cotransferred at a high frequency from
S. pyogenes
Spy005 and at very low frequencies from
S. pneumoniae
Spn529 and
S. pyogenes
Spy029.
Platelet Activation by Streptococcus pyogenes Leads to Entrapment in Platelet Aggregates, from Which Bacteria Subsequently Escape
Authors: Svensson Lisbeth , Baumgarten Maria , Mörgelin Matthias , Shannon Oonagh 
Published: July 2014

ABSTRACT

Platelet activation and aggregation have been reported to occur in response to a number of Gram-positive pathogens. Here, we show that platelet aggregates induced by
Streptococcus pyogenes
were unstable and that viable bacteria escaped from the aggregates over time. This was not due to differential activation in response to the bacteria compared with physiological activators. All the bacterial isolates induced significant platelet activation, including integrin activation and alpha and dense-granule release, at levels equivalent to those induced by potent physiological platelet activators that induced stable aggregates. The ability to escape the aggregates and to resist the antibacterial effects of platelets was dependent on active protein synthesis by the bacteria within the aggregate. We conclude that
S. pyogenes
bacteria can temporarily cover themselves with activated platelets, and we propose that this may facilitate survival of the bacteria in the presence of platelets.
Helicobacter pylori Infection Introduces DNA Double-Strand Breaks in Host Cells
Authors: Hanada Katsuhiro , Uchida Tomohisa , Tsukamoto Yoshiyuki , Watada Masahide , Yamaguchi Nahomi , Yamamoto Kaoru , Shiota Seiji , Moriyama Masatsugu , Graham David Y. , Yamaoka Yoshio 
Published: July 2014

ABSTRACT

Gastric cancer is an inflammation-related malignancy related to long-standing acute and chronic inflammation caused by infection with the human bacterial pathogen
Helicobacter pylori
. Inflammation can result in genomic instability. However, there are considerable data that
H. pylori
itself can also produce genomic instability both directly and through epigenetic pathways. Overall, the mechanisms of
H. pylori
-induced host genomic instabilities remain poorly understood. We used microarray screening of
H. pylori
-infected human gastric biopsy specimens to identify candidate genes involved in
H. pylori
-induced host genomic instabilities. We found upregulation of
ATM
expression
in vivo
in gastric mucosal cells infected with
H. pylori
. Using gastric cancer cell lines, we confirmed that the
H. pylori
-related activation of ATM was due to the accumulation of DNA double-strand breaks (DSBs). DSBs were observed following infection with both
cag
pathogenicity island (PAI)-positive and -negative strains, but the effect was more robust with
cag
PAI-positive strains. These results are consistent with the fact that infections with both
cag
PAI-positive and -negative strains are associated with gastric carcinogenesis, but the risk is higher in individuals infected with
cag
PAI-positive strains.
Coordinate Control of Virulence Gene Expression in Francisella tularensis Involves Direct Interaction between Key Regulators
Authors: Rohlfing Amy E. , Dove Simon L. 
Published: July 2014

ABSTRACT

In
Francisella tularensis
, the putative DNA-binding protein PigR works in concert with the SspA protein family members MglA and SspA to control the expression of genes that are essential for the intramacrophage growth and survival of the organism. MglA and SspA form a complex that interacts with RNA polymerase (RNAP), and this interaction between the MglA-SspA complex and RNAP is thought to be critical to its regulatory function. How PigR works in concert with the MglA-SspA complex is not known; previously published findings differ over whether PigR interacts with the MglA-SspA complex, leading to disparate models for how PigR and the MglA-SspA complex exert their regulatory effects. Here, using a combination of genetic assays, we identify mutants of MglA and SspA that are specifically defective for interaction with PigR. Analysis of the MglA and SspA mutants in
F. tularensis
reveals that interaction between PigR and the MglA-SspA complex is essential in order for PigR to work coordinately with MglA and SspA to positively regulate the expression of virulence genes. Our findings uncover a surface of the MglA-SspA complex that is important for interaction with PigR and support the idea that PigR exerts its regulatory effects through an interaction with the RNAP-associated MglA-SspA complex.
PI3K/mTOR Inhibition Markedly Potentiates HDAC Inhibitor Activity in NHL Cells through BIM- and MCL-1–Dependent Mechanisms In Vitro and In Vivo
Authors: Rahmani Mohamed , Aust Mandy Mayo , Benson Elisa C. , Wallace LaShanale , Friedberg Jonathan , Grant Steven 
Published: July 2014

Abstract
Purpose: The aim of this study is to explore the efficacy and define mechanisms of action of coadministration of the PI3K/mTOR inhibitor BEZ235 and pan-HDAC inhibitor panobinostat in diffuse large B-cell lymphoma (DLBCL) cells.
Experimental Design: Various DLBCL cells were exposed to panobinostat and BEZ235 alone or together after which apoptosis and signaling/survival pathway perturbations were monitored by flow cytometry and Western blot analysis. Genetic strategies defined the functional significance of such changes, and xenograft mouse models were used to assess tumor growth and animal survival.
Results: Panobinostat and BEZ235 interacted synergistically in ABC-, GC-, and double-hit DLBCL cells and MCL cells but not in normal CD34+ cells. Synergism was associated with pronounced AKT dephosphorylation, GSK3 dephosphorylation/activation, Mcl-1 downregulation, Bim upregulation, increased Bcl-2/Bcl-xL binding, diminished Bax/Bak binding to Bcl-2/Bcl-xL/Mcl-1, increased γH2A.X phosphorylation and histone H3/H4 acetylation, and abrogation of p21CIP1 induction. BEZ235/panobinostat lethality was not susceptible to stromal/microenvironmental forms of resistance. Genetic strategies confirmed significant functional roles for AKT inactivation, Mcl-1 downregulation, Bim upregulation, and Bax/Bak in synergism. Finally, coadministration of BEZ235 with panobinostat in immunocompromised mice bearing SU-DHL4–derived tumors significantly reduced tumor growth in association with similar signaling changes observed in vitro, and combined treatment increased animal survival compared with single agents.
Conclusions: BEZ235/panobinostat exhibits potent anti-DLBCL activity, including in poor-prognosis ABC- and double-hit subtypes, but not in normal CD34+ cells. Synergism is most likely multifactorial, involving AKT inactivation/GSK3 activation, Bim upregulation, Mcl-1 downregulation, enhanced DNA damage, and is operative in vivo. Combined PI3K/mTOR and HDAC inhibition warrants further attention in DLBCL. Clin Cancer Res; 20(18); 4849–60. ©2014 AACR.
Connecting the Time Series of Microwave Sounding Observations from AMSU to ATMS for Long-Term Monitoring of Climate
Authors: Zou Xiaolei , Weng Fuzhong , Yang H. 
Published: July 2014

Abstract
The measurements from the Microwave Sounding Unit (MSU) and the Advanced Microwave Sounding Unit-A (AMSU-A) on board NOAA polar-orbiting satellites have been extensively utilized for detecting atmospheric temperature trend during the last several decades. After the launch of the Suomi National Polar-orbiting Partnership (Suomi-NPP) satellite on 28 October 2011, MSU and AMSU-A time series will be overlapping with the Advanced Technology Microwave Sounder (ATMS) measurements. While ATMS inherited the central frequency and bandpass from most of AMSU-A sounding channels, its spatial resolution and noise features are, however, distinctly different from those of AMSU. In this study, the Backus–Gilbert method is used to optimally resample the ATMS data to AMSU-A fields of view (FOVs). The differences between the original and resampled ATMS data are demonstrated. By using the simultaneous nadir overpass (SNO) method, ATMS-resampled observations are collocated in space and time with AMSU-A data. The intersensor biases are then derived for each pair of ATMS–AMSU-A channels. It is shown that the brightness temperatures from ATMS now fall well within the AMSU data family after resampling and SNO cross calibration. Thus, the MSU–AMSU time series can be extended into future decades for more climate applications.
Paired immunoglobulin-like receptor B regulates platelet activation
Authors: Fan Xuemei , Shi Panlai , Dai Jing , Lu Yeling , Chen Xue , Liu Xiaoye , Zhang Kandi , Wu Xiaolin , Sun Yueping , Wang Kemin , Zhu Li , Zhang Cheng Cheng , Zhang Junfeng , Chen Guo-qiang , Zheng Junke , Liu Junling 
Published: July 2014

Key Points
Paired immunoglobulin-like receptor B negatively regulates platelet activation.
In Vivo Treatment Sensitivity Testing With Positron Emission Tomography/Computed Tomography After One Cycle of Chemotherapy for Hodgkin Lymphoma
Authors: Hutchings Martin , Kostakoglu Lale , Zaucha Jan Maciej , Malkowski Bogdan , Biggi Alberto , Danielewicz Iwona , Loft Annika , Specht Lena , Lamonica Dominick , Czuczman Myron S. , Nanni Christina , Zinzani Pier Luigi , Diehl Louis , Stern Richard , Coleman Morton 
Published: July 2014

Purpose Negative [18F]fluorodeoxyglucose (FDG) –positron emission tomography (PET)/computed tomography (CT) after two cycles of chemotherapy indicates a favorable prognosis in Hodgkin lymphoma (HL). We hypothesized that the negative predictive value would be even higher in patients responding rapidly enough to be PET negative after one cycle. This prospective study aimed to assess the prognostic value of PET after one cycle of chemotherapy in HL and to assess the dynamics of FDG uptake after one cycle (PET1) and after two cycles (PET2). Patients and Methods All PET scans were read by two blinded, independent reviewers in different countries, according to the Deauville five-point scale. The main end point was progression-free survival (PFS) after 2 years. Results A total of 126 patients were included, and all had PET1; 89 patients had both PET1 and PET2. The prognostic value of PET1 was statistically significant with respect to both PFS and overall survival. Two-year PFS for PET1-negative and PET1-positive patients was 94.1% and 40.8%, respectively. Among those with both PET1 and PET2, 2-year PFS was 98.3% and 38.5% for PET1-negative and PET1-positive patients and 90.2% and 23.1% for PET2-negative and PET2-positive patients, respectively. No PET1-negative patient was PET2 positive. Conclusion PET after one cycle of chemotherapy is highly prognostic in HL. No other prognostic tool identifies a group of patients with HL with a more favorable outcome than those patients with a negative PET1. In the absence of precise pretherapeutic predictive markers, PET1 is the best method for response-adapted strategies designed to select patients for less intensive treatment.
Improving Stability of Fire Fighting Foams by Water-Soluble Polymers
Authors: Любимов  , Lyubimov Viktor , Скушникова  , Skushnikova Alvira 
Published: July 2014

The article studies the effect of polymeric stabilizing additives on stability, expansion ratio, and complete destruction
period of foams derived from aqueous solutions of surfactants. Use of additives such as poliviniltriazole, polyethylene
oxide, and polymethacrylic acid is proven to correlate foam stability and period of its complete degradation to the kind
of the polymer and its molar mass. Moreover, usage of acrylamide polymers as additives to biologically soft industrial
foam formers improves stability of fire-fighting foams. It was established that polyacrylamide of М=107 molecular weight
has the highest stabilizing effect on fire-fighting foams. Foam agents with polyacrylamide additives provide for 5 times
decrease of extinguishment period of flammable liquids compared to extinguishment period without polyacrylamide
additives.
Occupational Illness: Current State, Problems and Improvement of Diagnostics
Authors: Ретнев  , Retnev V. 
Published: July 2014

The paper investigates reasons for poor quality of occupational illnesses detection in Russia in comparison with foreign
countries. Today a considerable amount of work-related diseases are not diagnosed and registered because of reluctance of
employers, poor performance of medical boards, and low skill level of occupational pathology medical workers.
Delirium in older people in hospital: an education programme
Authors: Varghese Nibi C , Macaden Leah , Premkumar Beulah , Mathews Prasad , Kumar Saravanan 
Published: July 2014

Aim: This study aimed to determine the effectiveness of an educational programme on the identification and management of delirium by nurses in the medical wards of a tertiary care hospital in South India. Method: A non-equivalent controlled pre- and post-intervention research design was used. The sample size of nurses through convenient sampling was 15 in the experimental group and 17 in the comparison group. A questionnaire was used to assess the knowledge of nurses and an observation checklist was used to assess practice. The Confusion Assessment Method ( Inouye et al, 1990 ) was used to detect delirium among older people who were hospitalised. Data collection was carried out over a 6-week period. Results: There was a significant improvement in the knowledge (p<0.001) and practice (p<0.003) of nurses in the experimental group following the educational programme.
Standards for Pediatric Cancer Centers
Authors:   SECTION ON HEMATOLOGY/ONCOLOGY, Hord Jeffrey , Feig Stephen , Crouch Gary , Hale Gregory , Mueller Brigitta , Rogers Zora , Shearer Patricia , Werner Eric 
Published: July 2014

This Policy Statement was reaffirmed October 2018.
Since the American Academy of Pediatrics–published guidelines for pediatric cancer centers in 1986, 1997, and 2004, significant changes in the delivery of health care have prompted a review of the role of medical centers in the care of pediatric patients. The potential effect of these changes on the treatment and survival rates of children with cancer led to this revision. The intent of this statement is to delineate personnel, capabilities, and facilities that are essential to provide state-of-the-art care for children, adolescents, and young adults with cancer. This statement emphasizes the importance of board-certified pediatric hematologists/oncologists and appropriately qualified pediatric medical subspecialists and pediatric surgical specialists overseeing patient care and the need for specialized facilities as essential for the initial management and much of the follow-up for pediatric, adolescent, and young adult patients with cancer. For patients without practical access to a pediatric cancer center, care may be provided locally by a primary care physician or adult oncologist but at the direction of a pediatric oncologist.