bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibiotic Resistance as a Stress Response: Recovery of High-Level Oxacillin Resistance in Methicillin-Resistant Staphylococcus aureus “Auxiliary” (
fem
) Mutants by Induction of the Stringent Stress Response
Authors: Kim Choon Keun , Milheiriço Catarina , de Lencastre Hermínia , Tomasz Alexander
Published: June 2017

Studies with methicillin-resistant
Staphylococcus aureus
(MRSA) strain COL have shown that the optimal resistance phenotype requires not only
mecA
but also a large number of “auxiliary genes” identified by Tn
551
mutagenesis. The majority of auxiliary mutants showed greatly increased levels of oxacillin resistance when grown in the presence of sub-MICs of mupirocin, suggesting that the mechanism of reduced resistance in the auxiliary mutants involved the interruption of a stringent stress response, causing reduced production of penicillin-binding protein 2A (PBP 2A).
Pharmacodynamics and Biodistribution of Single-Dose Liposomal Amphotericin B at Different Stages of Experimental Visceral Leishmaniasis
Authors: Voak Andrew A. , Harris Andy , Qaiser Zeeshan , Croft Simon L. , Seifert Karin
Published: June 2017

Visceral leishmaniasis is a neglected tropical disease that causes significant morbidity and mortality worldwide. Characterization of the pharmacokinetics and pharmacodynamics of antileishmanial drugs in preclinical models is important for drug development and use. Here we investigated the pharmacodynamics and drug distribution of liposomal amphotericin B (AmBisome) in
Leishmania donovani
-infected BALB/c mice at three different dose levels and two different time points after infection. We additionally compared drug levels in plasma, liver, and spleen in infected and uninfected BALB/c mice over time. At the highest administered dose of 10 mg/kg AmBisome, >90% parasite inhibition was observed within 2 days after drug administration, consistent with drug distribution from blood to tissue within 24 h and a fast rate of kill. Decreased drug potency was observed in the spleen when AmBisome was administered on day 35 after infection, compared to day 14 after infection. Amphotericin B concentrations and total drug amounts per organ were lower in liver and spleen when AmBisome was administered at the advanced stage of infection and compared to those in uninfected BALB/c mice. However, the magnitude of difference was lower when total drug amounts per organ were estimated. Differences were also noted in drug distribution to
L. donovani
-infected livers and spleens. Taken together, our data suggest that organ enlargement and other pathophysiological factors cause infection- and organ-specific drug distribution and elimination after administration of single-dose AmBisome to
L. donovani
-infected mice. Plasma drug levels were not reflective of changes in drug levels in tissues.
Genomewide Analysis of the Antimicrobial Peptides in Python bivittatus and Characterization of Cathelicidins with Potent Antimicrobial Activity and Low Cytotoxicity
Authors: Kim Dayeong , Soundrarajan Nagasundarapandian , Lee Juyeon , Cho Hye-sun , Choi Minkyeung , Cha Se-Yeoun , Ahn Byeongyong , Jeon Hyoim , Le Minh Thong , Song Hyuk , Kim Jin-Hoi , Park Chankyu
Published: June 2017

In this study, we sought to identify novel antimicrobial peptides (AMPs) in
Python bivittatus
through bioinformatic analyses of publicly available genome information and experimental validation. In our analysis of the python genome, we identified 29 AMP-related candidate sequences. Of these, we selected five cathelicidin-like sequences and subjected them to further
in silico
analyses. The results showed that these sequences likely have antimicrobial activity. The sequences were named Pb-CATH1 to Pb-CATH5 according to their sequence similarity to previously reported snake cathelicidins. We predicted their molecular structure and then chemically synthesized the mature peptide for three putative cathelicidins and subjected them to biological activity tests. Interestingly, all three peptides showed potent antimicrobial effects against Gram-negative bacteria but very weak activity against Gram-positive bacteria. Remarkably, ΔPb-CATH4 showed potent activity against antibiotic-resistant clinical isolates and also was observed to possess very low hemolytic activity and cytotoxicity. ΔPb-CATH4 also showed considerable serum stability. Electron microscopic analysis indicated that ΔPb-CATH4 exerts its effects via toroidal pore preformation. Structural comparison of the cathelicidins identified in this study to previously reported ones revealed that these Pb-CATHs are representatives of a new group of reptilian cathelicidins lacking the acidic connecting domain. Furthermore, Pb-CATH4 possesses a completely different mature peptide sequence from those of previously described reptilian cathelicidins. These new AMPs may be candidates for the development of alternatives to or complements of antibiotics to control multidrug-resistant pathogens.
Efficacy of Cefiderocol against Carbapenem-Resistant Gram-Negative Bacilli in Immunocompetent-Rat Respiratory Tract Infection Models Recreating Human Plasma Pharmacokinetics
Authors: Matsumoto Shuhei , Singley Christine M. , Hoover Jennifer , Nakamura Rio , Echols Roger , Rittenhouse Stephen , Tsuji Masakatsu , Yamano Yoshinori
Published: June 2017

Cefiderocol (S-649266), a novel siderophore cephalosporin, shows potent activity against carbapenem-resistant Gram-negative bacilli. In this study, we evaluated the efficacy of cefiderocol against carbapenem-resistant Gram-negative bacilli (
Pseudomonas aeruginosa
,
Acinetobacter baumannii
, and
Klebsiella pneumoniae
) in immunocompetent-rat respiratory tract infection models recreating plasma pharmacokinetics (PK) profiles in healthy human subjects. A total of 6 clinical isolates (1 cephalosporin-susceptible
P. aeruginosa
isolate, 1 multidrug-resistant
P. aeruginosa
isolate, 2 multidrug-resistant
A. baumannii
isolates, and 2 carbapenem-resistant
K. pneumoniae
isolates) were evaluated. Four-day treatment with a human exposure of 1 g ceftazidime every 8 h as a 0.5-h infusion showed potent efficacy only against a ceftazidime-susceptible isolate, not against five ceftazidime-resistant isolates harboring carbapenemase. With cefiderocol, a human exposure of 2 g every 8 h as a 3-h infusion for 4 days produced a >3 log
10
reduction in the number of viable cells of these carbapenem-resistant isolates in the lungs. When the infusion time was 1 h, bactericidal activity was also observed against all isolates tested, although for 2 of 5 carbapenem-resistant isolates, a 3 log
10
reduction was not achieved. The difference in efficacy achieved by changing the infusion period from 1 h to 3 h was considered to be due to the higher percentage of the dosing interval during which free-drug concentrations were above the MIC (%
fT
MIC
), as observed for β-lactam antibiotics. These results suggest the potential utility of cefiderocol for the treatment of lung infections caused by carbapenem-resistant
P. aeruginosa
,
A. baumannii
, and
K. pneumoniae
strains.
De Novo
Acquisition of Resistance to SCY-078 in Candida glabrata Involves FKS Mutations That both Overlap and Are Distinct from Those Conferring Echinocandin Resistance
Authors: Jiménez-Ortigosa Cristina , Perez Winder B. , Angulo David , Borroto-Esoda Katyna , Perlin David S.
Published: June 2017

SCY-078 is an orally active antifungal whose target is the β-(1,3)-
d
-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078-resistant
Candida glabrata
isolates following drug exposure
in vitro
. Resistant isolates were analyzed using broth microdilution methodology and
FKS
sequencing. The kinetic inhibition parameter IC
50
(50% inhibitory concentration) was also determined from GS complexes. The spectrum of resistance mutations found suggested a partially overlapping but independent binding site for SCY-078 relative to echinocandins on GS.
Identification of 1-((2,4-Dichlorophenethyl)Amino)-3-Phenoxypropan-2-ol, a Novel Antibacterial Compound Active against Persisters of Pseudomonas aeruginosa
Authors: Liebens Veerle , Defraine Valerie , Knapen Wouter , Swings Toon , Beullens Serge , Corbau Romu , Marchand Arnaud , Chaltin Patrick , Fauvart Maarten , Michiels Jan
Published: June 2017

Antibiotics typically fail to completely eradicate a bacterial population, leaving a small fraction of transiently antibiotic-tolerant persister cells intact. Persisters are therefore seen to be a major cause of treatment failure and greatly contribute to the recalcitrant nature of chronic infections. The current study focused on
Pseudomonas aeruginosa
, a Gram-negative pathogen belonging to the notorious ESKAPE group of pathogens (
Enterococcus faecium
,
Staphylococcus aureus
,
Klebsiella pneumoniae
,
Acinetobacter baumannii
,
Pseudomonas aeruginosa
, and
Enterobacter
species) and, due to increasing resistance against most conventional antibiotics, posing a serious threat to human health. Greatly contributing to the difficult treatment of
P. aeruginosa
infections is the presence of persister cells, and elimination of these cells would therefore significantly improve patient outcomes. In this study, a small-molecule library was screened for compounds that, in combination with the fluoroquinolone antibiotic ofloxacin, reduced the number of
P. aeruginosa
persisters compared to the number achieved with treatment with the antibiotic alone. Based on the early structure-activity relationship, 1-((2,4-dichlorophenethyl)amino)-3-phenoxypropan-2-ol (SPI009) was selected for further characterization. Combination of SPI009 with mechanistically distinct classes of antibiotics reduced the number of persisters up to 10
6
-fold in both lab strains and clinical isolates of
P. aeruginosa
. Further characterization of the compound revealed a direct and efficient killing of persister cells. SPI009 caused no erythrocyte damage and demonstrated minor cytotoxicity. In conclusion, we identified a novel antipersister compound active against
P. aeruginosa
with promising applications for the design of novel, case-specific combination therapies in the fight against chronic infections.
Bioavailability of Lumefantrine Is Significantly Enhanced with a Novel Formulation Approach, an Outcome from a Randomized, Open-Label Pharmacokinetic Study in Healthy Volunteers
Authors: Jain Jay Prakash , Leong F. Joel , Chen Lan , Kalluri Sampath , Koradia Vishal , Stein Daniel S. , Wolf Marie-Christine , Sunkara Gangadhar , Kota Jagannath
Published: June 2017

The artemether-lumefantrine combination requires food intake for the optimal absorption of lumefantrine. In an attempt to enhance the bioavailability of lumefantrine, new solid dispersion formulations (SDF) were developed, and the pharmacokinetics of two SDF variants were assessed in a randomized, open-label, sequential two-part study in healthy volunteers. In part 1, the relative bioavailability of the two SDF variants was compared with that of the conventional formulation after administration of a single dose of 480 mg under fasted conditions in three parallel cohorts. In part 2, the pharmacokinetics of lumefantrine from both SDF variants were evaluated after a single dose of 480 mg under fed conditions and a single dose of 960 mg under fasted conditions. The bioavailability of lumefantrine from SDF variant 1 and variant 2 increased up to ∼48-fold and ∼24-fold, respectively, relative to that of the conventional formulation. Both variants demonstrated a positive food effect and a less than proportional increase in exposure between the 480-mg and 960-mg doses. Most adverse events (AEs) were mild to moderate in severity and not suspected to be related to the study drug. All five drug-related AEs occurred in subjects taking SDF variant 2. No clinically significant treatment-emergent changes in vital signs, electrocardiograms, or laboratory blood assessments were noted. The solid dispersion formulation enhances the lumefantrine bioavailability to a significant extent, and SDF variant 1 is superior to SDF variant 2.
Antimicrobial Susceptibility Trends among Staphylococcus aureus Isolates from U.S. Hospitals: Results from 7 Years of the Ceftaroline (AWARE) Surveillance Program, 2010 to 2016
Authors: Sader Helio S. , Mendes Rodrigo E. , Streit Jennifer M. , Flamm Robert K.
Published: June 2017

We evaluated trends in
Staphylococcus aureus
antimicrobial susceptibility in U.S. hospitals in the 2010–2016 period. A total of 21,056 clinical isolates from 42 medical centers were tested for susceptibility by broth microdilution methods. Methicillin-resistant
S. aureus
(MRSA) rates decreased from 50.0% (in 2010) to 42.2% (in 2016). Susceptibility to erythromycin, levofloxacin, and clindamycin increased slightly, whereas susceptibility to ceftaroline, trimethoprim-sulfamethoxazole, and tetracycline remained stable. Ceftaroline retained potent activity against methicillin-susceptible
S. aureus
(MSSA) and MRSA (97.2% susceptible) with no marked variations.
Biodistribution and
In Vivo
Antileishmanial Activity of 1,2-Distigmasterylhemisuccinoyl-
sn
-Glycero-3-Phosphocholine Liposome-Intercalated Amphotericin B
Authors: Iman Maryam , Huang Zhaohua , Alavizadeh Seyedeh Hoda , Szoka Francis C. , Jaafari Mahmoud R.
Published: June 2017

1,2-Distigmasterylhemisuccinoyl-
sn
-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that liposome (Lip)-intercalated amphotericin B (AMB) prepared from DSHemsPC (DSHemsPC-AMB-Lip) possesses excellent colloidal properties and
in vitro
antifungal and antileishmanial activities similar to those of the liposomal AMB preparation AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of DSHemsPC-AMB-Lip in
Leishmania major
-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in DSHemsPC-AMB-Lip- and AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (Fungizone; 1 mg/kg of body weight), DSHemsPC-AMB-Lip (5 mg/kg), and AmBisome (5 mg/kg) were used in
L. major
-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of cutaneous leishmaniasis (CL), the results indicated that the level of footpad inflammation was significantly (
P
< 0.001) lower in mice treated with DSHemsPC-AMB-Lip and AmBisome than mice treated with empty liposomes or 5% dextrose. The splenic and footpad parasite load was also significantly (
P
< 0.001) lower in these groups of mice than in control mice that received 5% DW or free liposome. The
in vivo
activity of DSHemsPC-AMB-Lip was comparable to that of AmBisome, and both provided improved results compared to those achieved with Fungizone at the designated doses. The results suggest that systemic DSHemsPC-AMB-Lip administration may be useful for the treatment of leishmaniasis, and because it costs less to produce DSHemsPC-AMB-Lip than AmBisome, DSHemsPC-AMB-Lip merits further investigation.
Albumin Inhibits Pseudomonas aeruginosa Quorum Sensing and Alters Polymicrobial Interactions
Authors: Smith Allie Clinton , Rice Anne , Sutton Bryan , Gabrilska Rebecca , Wessel Aimee K. , Whiteley Marvin , Rumbaugh Kendra P.
Published: June 2017

Polymicrobial interactions are complex and can influence the course of an infection, as is the case when two or more species exhibit a synergism that produces a disease state not seen with any of the individual species alone. Cell-to-cell signaling is key to many of these interactions, but little is understood about how the host environment influences polymicrobial interactions or signaling between bacteria. Chronic wounds are typically polymicrobial, with
Staphylococcus aureus
and
Pseudomonas aeruginosa
being the two most commonly isolated species. While
P. aeruginosa
readily kills
S. aureus
in vitro
, the two species can coexist for long periods together in chronic wound infections. In this study, we investigated the ability of components of the wound environment to modulate interactions between
P. aeruginosa
and
S. aureus
. We demonstrate that
P. aeruginosa
quorum sensing is inhibited by physiological levels of serum albumin, which appears to bind and sequester some homoserine lactone quorum signals, resulting in the inability of
P. aeruginosa
to produce virulence factors that kill
S. aureus
. These data could provide important clues regarding the virulence of
P. aeruginosa
in albumin-depleted versus albumin-rich infection sites and an understanding of the nature of friendly versus antagonistic interactions between
P. aeruginosa
and
S. aureus
.
Pneumolysin-Dependent Calpain Activation and Interleukin-1α Secretion in Macrophages Infected with Streptococcus pneumoniae
Authors: Fang Rendong , Wu Rui , Du Huihui , Jin Meilan , Liu Yajing , Lei Guihua , Jiang Bing , Lei Zehui , Peng Yuanyi , Nie Kui , Tsuchiya Kohsuke
Published: June 2017

Pneumolysin (PLY), a major virulence factor of
Streptococcus pneumoniae
, is a pore-forming cytolysin that modulates host innate responses contributing to host defense against and pathogenesis of pneumococcal infections. Interleukin-1α (IL-1α) has been shown to be involved in tissue damage in a pneumococcal pneumonia model; however, the mechanism by which this cytokine is produced during
S. pneumoniae
infection remains unclear. In this study, we examined the role of PLY in IL-1α production. Although the strains induced similar levels of pro-IL-1α expression, wild-type
S. pneumoniae
D39, but not a deletion mutant of the
ply
gene (Δ
ply
), induced the secretion of mature IL-1α from host macrophages, suggesting that PLY is critical for the maturation and secretion of IL-1α during
S. pneumoniae
infection. Further experiments with calcium chelators and calpain inhibitors indicated that extracellular calcium ions and calpains (calcium-dependent proteases) facilitated the maturation and secretion of IL-1α from D39-infected macrophages. Moreover, we found that PLY plays a critical role in calcium influx and calpain activation, as elevated intracellular calcium levels and the degradation of the calpain substrate α-fodrin were detected in macrophages infected with D39 but not the Δ
ply
strain. These results suggested that PLY induces the influx of calcium in
S. pneumoniae
-infected macrophages, followed by calpain activation and subsequent IL-1α maturation and secretion.
CCR5 Is Involved in Interruption of Pregnancy in Mice Infected with Toxoplasma gondii during Early Pregnancy
Authors: Nishimura Maki , Umeda Kousuke , Suwa Masayuki , Furuoka Hidefumi , Nishikawa Yoshifumi
Published: June 2017

Toxoplasmosis can cause abortion in pregnant humans and other animals; however, the mechanism of abortion remains unknown. C-C chemokine receptor type 5 (CCR5) is essential for host defense against
Toxoplasma gondii
infection. To investigate the relationship between CCR5 and abortion in toxoplasmosis, we inoculated wild-type and CCR5-deficient (CCR5
−/−
) mice with
T. gondii
tachyzoites intraperitoneally on day 3 of pregnancy (embryonic day 3 [E3]). The pregnancy rate decreased as pregnancy progressed in infected wild-type mice. Histopathologically, no inflammatory lesions were observed in the fetoplacental tissues. Although wild-type mice showed a higher parasite burden at the implantation sites than did CCR5
−/−
mice at E6 (3 days postinfection [dpi]),
T. gondii
antigen was detected only in the uterine tissue and not in the fetoplacental tissues. At E8 (5 dpi), the embryos in infected wild-type mice showed poor development compared with those of infected CCR5
−/−
mice, and apoptosis was observed in poorly developed embryos. Compared to uninfected mice, infected wild-type mice showed increased CCR5 expression at the implantation site at E6 and E8. Furthermore, analyses of mRNA expression in the uterus of nonpregnant and pregnant mice suggested that a lack of the
CCR5
gene and the downregulation of tumor necrosis factor alpha (TNF-α) and CCL3 expression at E6 (3 dpi) are important factors for the maintenance of pregnancy following
T. gondii
infection. These results suggested that CCR5 signaling is involved in embryo loss in
T. gondii
infection during early pregnancy and that apoptosis is associated with embryo loss rather than direct damage to the fetoplacental tissues.
How a Genetically Stable Extremophile Evolves: Modes of Genome Diversification in the Archaeon Sulfolobus acidocaldarius
Authors: Mao Dominic , Grogan Dennis W.
Published: June 2017

In order to analyze in molecular terms howSulfolobusgenomes diverge, damage-induced mutations and natural polymorphisms (PMs) were identified in laboratory constructs and wild-type isolates, respectively, ofSulfolobus acidocaldarius. Among wild-type isolates drawn from one local population, pairwise nucleotide divergence averaged 4 × 10−6, which is about 0.15% of the corresponding divergence reported forSulfolobus islandicus. The most variable features of wild-typeS. acidocaldariusgenomes were homopolymer (mononucleotide) tracts and longer tandem repeats, consistent with the spontaneous mutations that occur under laboratory conditions. Natural isolates, however, also revealed large insertions/deletions and inversions, which did not occur in any of the laboratory-manipulated strains. Several of the large insertions/deletions could be attributed to the integration or excision of mobile genetic elements (MGEs), and each MGE represented a distinct system of site-specific recombination. The mode of recombination associated with one MGE, a provirus related toSulfolobus turreted icosahedral virus, was also seen in certain chromosomal inversions. Artificially induced mutations, non-MGE insertions/deletions, and small PMs exhibited different distributions over the genome, suggesting that large-scale patterning ofSulfolobusgenomes begins early in the divergence process. Unlike induced mutations, natural base pair substitutions occurred in clusters, and one cluster exhibited properties expected of nonreciprocal recombination (gene conversion) between dispersed imperfect repeats. Taken together, the results identify simple replication errors, slipped-strand events promoted by tandem repeats, homologous recombination, and rearrangements promoted by MGEs as the primary sources of genetic variation for this extremely acidophilic archaeon in its geothermal environment.

IMPORTANCEThe optimal growth temperatures of hyperthermophilic archaea accelerate DNA decomposition, which is expected to make DNA repair especially important for their genetic stability, yet these archaea lack certain broadly conserved types of DNA repair proteins. In this study, the genome of the extreme thermoacidophileSulfolobus acidocaldariuswas found to be remarkably stable, accumulating few mutations in many (though not all) laboratory manipulations and in natural populations. Furthermore, all the genetic processes that were inferred to diversify these genomes also operate in mesophilic bacteria and eukaryotes. This suggests that a common set of mechanisms produces most of the genetic variation in all microorganisms, despite the fundamental differences in physiology, DNA repair systems, and genome structure represented in the three domains of life.
Identification of a
d
-Arabinose-5-Phosphate Isomerase in the Gram-Positive Clostridium tetani
Authors: Cech David L. , Markin Katherine , Woodard Ronald W.
Published: June 2017

d
-Arabinose-5-phosphate (A5P) isomerases (APIs) catalyze the interconversion of
d
-ribulose-5-phosphate and
d
-arabinose-5-phosphate. Various Gram-negative bacteria, such as the uropathogenic
Escherichia coli
strain CFT073, contain multiple API paralogs (KdsD, GutQ, KpsF, and c3406) that have been assigned various cellular functions. The
d
-arabinose-5-phosphate formed by these enzymes seems to play important roles in the biosynthesis of lipopolysaccharide (LPS) and group 2 K-antigen capsules, as well as in the regulation of the cellular
d
-glucitol uptake and uropathogenic infectivity/virulence. The genome of a Gram-positive pathogenic bacterium,
Clostridium tetani
, contains a gene encoding a putative API,
C. tetani
API (CtAPI), even though
C. tetani
lacks both LPS and capsid biosynthetic genes. To better understand the physiological role of
d
-arabinose-5-phosphate in this Gram-positive organism, recombinant CtAPI was purified and characterized. CtAPI displays biochemical characteristics similar to those of APIs from Gram-negative organisms and complements the API deficiency of an
E. coli
API knockout strain. Thus, CtAPI represents the first
d
-arabinose-5-phosphate isomerase to be identified and characterized from a Gram-positive bacterium.

IMPORTANCE
The genome of
Clostridium tetani
, a pathogenic Gram-positive bacterium and the causative agent of tetanus, contains a gene (the CtAPI gene) that shares high sequence similarity with those of genes encoding
d
-arabinose-5-phosphate isomerases. APIs play an important role within Gram-negative bacteria in
d
-arabinose-5-phosphate production for lipopolysaccharide biosynthesis, capsule formation, and regulation of cellular
d
-glucitol uptake. The significance of our research is in identifying and characterizing CtAPI, the first Gram-positive API. Our findings show that CtAPI is specific to the interconversion of arabinose-5-phosphate and ribulose-5-phosphate while having no activity with the other sugars and sugar phosphates tested. We have speculated a regulatory role for this API in
C. tetani
, an organism that does not produce lipopolysaccharide.
A Key Enzyme of the NAD
+
Salvage Pathway in Thermus thermophilus: Characterization of Nicotinamidase and the Impact of Its Gene Deletion at High Temperatures
Authors: Taniguchi Hironori , Sungwallek Sathidaphorn , Chotchuang Phatcharin , Okano Kenji , Honda Kohsuke
Published: June 2017

NAD (NAD
+
) is a cofactor related to many cellular processes. This cofactor is known to be unstable, especially at high temperatures, where it chemically decomposes to nicotinamide and ADP-ribose. Bacteria, yeast, and higher organisms possess the salvage pathway for reconstructing NAD
+
from these decomposition products; however, the importance of the salvage pathway for survival is not well elucidated, except for in pathogens lacking the NAD
+
de novo
synthesis pathway. Herein, we report the importance of the NAD
+
salvage pathway in the thermophilic bacterium
Thermus thermophilus
HB8 at high temperatures. We identified the gene encoding nicotinamidase (TTHA0328), which catalyzes the first reaction of the NAD
+
salvage pathway. This recombinant enzyme has a high catalytic activity against nicotinamide (

K
m

of 17 μM,
k
cat
of 50 s
−1
,
k
cat
/

K
m

of 3.0 × 10
3
s
−1
· mM
−1
). Deletion of this gene abolished nicotinamide deamination activity in crude extracts of
T. thermophilus
and disrupted the NAD
+
salvage pathway in
T. thermophilus
. Disruption of the salvage pathway led to the severe growth retardation at a higher temperature (80°C), owing to the drastic decrease in the intracellular concentrations of NAD
+
and NADH.

IMPORTANCE
NAD
+
and other nicotinamide cofactors are essential for cell metabolism. These molecules are unstable and decompose, even under the physiological conditions in most organisms. Thermophiles can survive at high temperatures where NAD
+
decomposition is, in general, more rapid. This study emphasizes that NAD
+
instability and its homeostasis can be one of the important factors for thermophile survival in extreme temperatures.
Comparison of Electroacupuncture and Medical Treatment for Functional Constipation: A Systematic Review and Meta-Analysis
Authors: Zhou Sheng-Li , Zhang Xiu-Lai , Wang Jing-Hua
Published: June 2017

Objectives

To assess the effectiveness of electroacupuncture (EA) relative to conventional medication in functional constipation (FC).

Design

Systematic review and meta-analysis.

Setting

To be included, studies needed to: (1) have been randomised controlled trials; (2) have recruited adult patients diagnosed with FC according to the Rome II/III criteria or the American Gastroenterological Association guideline for chronic FC; and (3) have randomised patients to be treated with EA or anti-constipation medication. We searched Medline, the Cochrane Library and Embase databases for articles published up to 30 June 2016.

Intervention

EA or anti-constipation medication.

Primary and secondary outcome measures

The primary outcome was the change in the number of weekly spontaneous bowel movements. Secondary outcomes were total response rate (or total effective rate), symptom reduction and Cleveland Clinic constipation scores.

Results

The pooled results showed significantly more improvement in the frequency of spontaneous bowel movements in the EA treatment group compared with the medicine-treated group (pooled SMD 0.244, 95% CI 0.065 to 0.424, P=0.008). Deep-needling EA was significantly more effective than treatment with medication at increasing the frequency of spontaneous bowel movements (p=0.019). Significantly greater improvement was also seen for total response rates (p=0.018) and reductions in symptom score (p<0.001) in EA-treated patients.

Conclusions

EA was more effective than medication at improving spontaneous bowel movements and total response rate, and reducing the symptoms of FC.
Pre-eclampsia and the risk of retinopathy of prematurity in preterm infants with birth weight <1500 g and/or <31 weeks’ gestation
Authors: Alshaikh Belal , Salman Omar , Soliman Nancy , Ells Anna , Yusuf Kamran
Published: June 2017

Objective

To evaluate the relationship between pre-eclampsia and development of retinopathy of prematurity (ROP) in infants with birth weight of <1500 g and/or gestation <31 weeks.

Methods

A retrospective cohort study comprising infants born to mothers with pre-eclampsia between January 2007 and June 2010 at a single tertiary care centre. Their ROP outcome was compared with infants born to the next two normotensive mothers with a ±1 week gestational age difference. Pearson χ2test was used for categorical variables and Mann-Whitney U test was used for continuous variables. Multivariable regression was used to estimate the OR of ROP with prenatal pre-eclampsia exposure and adjust for confounders.

Results

Of the 97 infants in the pre-eclampsia group, 27 (27%) developed ROP and of the 185 infants in the normotensive group, 50 (27%) developed ROP. On multivariable regression modelling, pre-eclampsia was not a risk factor for the development of ROP (OR 1.4, 95% CI 0.46 to 4.1). Gestational age, intrauterine growth restriction and blood transfusion were significant risk factors for the development of ROP.

Conclusions

In our cohort, pre-eclampsia was not a significant risk factor for the development of ROP. Intrauterine growth restricted infants of pre-eclamptic and normotensive mothers were at higher risk of ROP.
Thermal Behavior and Spectroscopy Analysis of Carbonized Nanostructures Derived from Polypyrrole Nanotubes
Authors: Fracari Tiago , Einloft Sandra , Lavayen Vladimir
Published: June 2017

Carbonaceous nanotubes with a calculated specific heat of 710[Formula: see text]J K[Formula: see text] Kg[Formula: see text], and an outer diameter of 58[Formula: see text]nm, made by a micro-thermal reaction, using polypyrrole nanotubes precursor is presented here. Three degradation stages from the thermal curves are identified. We observe a decomposition temperature at 371[Formula: see text]C that relates to the presence of amorphous carbon on samples for the first time in this material. Also, it is identified that gradual decomposition of the fragments provides a different kind of residue percentage in the range 48–32% that is related to stirring speed used in each synthesis. It is worthy to note that electron transmission microscope images of carbonaceous nanotubes present defects as well, wherein we identify chloride and nitrogen as doped agents. Finally, results of nanotubes using Infrared, Raman spectrometry analysis, scanning electron microscopy and electron diffraction are presented here.
Comparative Analysis of the Cell Fates of Induced Schwann Cells from Subcutaneous Fat Tissue and Naïve Schwann Cells in the Sciatic Nerve Injury Model
Authors: Zhang Mingzi , Jiang Mei Hua , Kim Dae-Wook , Ahn Woosung , Chung Eunkyung , Son Youngsook , Chi Guangfan
Published: June 2017

Purpose. The fate and function of the induced Schwann cells (iSCs) like cells from adipose tissue have not been critically evaluated in vivo after transplantation. The objective of this study is to compare the fate of iSCs with naïve SCs (nSCs) after transplantation into the lesion sites of sciatic nerve, respectively. Methods. Adipose-derived stem cells from eGFP-expressing transgenic rat’s subcutaneous fat were induced to iSCs in vitro. iSCs were injected to the sciatic nerve lesion area after crush injury and the cells fate was comparatively analyzed with that of nSCs from the same rat. Results. At 12 weeks after transplantation, nSCs were detected only in the restricted area of cell transplantation site but iSCs were widely distributed all over the sciatic nerve. Based on double fluorescence observations, both iSCs and naïve ones were colocalized with P0-expressing myelin sheath, outbound by laminin-expressing basal membrane, and terminated at contactin-associated protein-expressing doublets. However, some of iSCs were also differentiated to the fibrocyte/fibroblast-like cells. In the histological analysis of repaired sciatic nerves, axon density was higher in iSC-received group than in the nSCs group and normal sciatic nerve. Conclusion. iSCs induced from subcutaneous fat tissues have higher engraftment and migration capacity than nSCs.
The Astrocytic S100B Protein with Its Receptor RAGE Is Aberrantly Expressed in SOD1G93A Models, and Its Inhibition Decreases the Expression of Proinflammatory Genes
Authors: Serrano Alessia , Donno Claudia , Giannetti Stefano , Perić Mina , Andjus Pavle , D’Ambrosi Nadia , Michetti Fabrizio
Published: June 2017

Neuroinflammation is one of the major players in amyotrophic lateral sclerosis (ALS) pathogenesis, and astrocytes are significantly involved in this process. The astrocytic protein S100B can be released in pathological states activating the receptor for advanced glycation end products (RAGE). Different indications point to an aberrant expression of S100B and RAGE in ALS. In this work, we observed that S100B and RAGE are progressively and selectively upregulated in astrocytes of diseased rats with a tissue-specific timing pattern, correlated to the level of neurodegeneration. The expression of the full-length and soluble RAGE isoforms could also be linked to the degree of tissue damage. The mere presence of mutant SOD1 is able to increase the intracellular levels and release S100B from astrocytes, suggesting the possibility that an increased astrocytic S100B expression might be an early occurring event in the disease. Finally, our findings indicate that the protein may exert a proinflammatory role in ALS, since its inhibition in astrocytes derived from SOD1G93A mice limits the expression of reactivity-linked/proinflammatory genes. Thus, our results propose the S100B-RAGE axis as an effective contributor to the pathogenesis of the disease, suggesting its blockade as a rational target for a therapeutic intervention in ALS.
Inexact Multistage Stochastic Chance Constrained Programming Model for Water Resources Management under Uncertainties
Authors: Zhang Hong , Ha Minghu , Zhao Hongyu , Song Jianwei
Published: June 2017

In order to formulate water allocation schemes under uncertainties in the water resources management systems, an inexact multistage stochastic chance constrained programming (IMSCCP) model is proposed. The model integrates stochastic chance constrained programming, multistage stochastic programming, and inexact stochastic programming within a general optimization framework to handle the uncertainties occurring in both constraints and objective. These uncertainties are expressed as probability distributions, interval with multiply distributed stochastic boundaries, dynamic features of the long-term water allocation plans, and so on. Compared with the existing inexact multistage stochastic programming, the IMSCCP can be used to assess more system risks and handle more complicated uncertainties in water resources management systems. The IMSCCP model is applied to a hypothetical case study of water resources management. In order to construct an approximate solution for the model, a hybrid algorithm, which incorporates stochastic simulation, back propagation neural network, and genetic algorithm, is proposed. The results show that the optimal value represents the maximal net system benefit achieved with a given confidence level under chance constraints, and the solutions provide optimal water allocation schemes to multiple users over a multiperiod planning horizon.
Extinction and Persistence in Mean of a Novel Delay Impulsive Stochastic Infected Predator-Prey System with Jumps
Authors: Liu Guodong , Wang Xiaohong , Meng Xinzhu , Gao Shujing
Published: June 2017

In this paper, we explore an impulsive stochastic infected predator-prey system with Lévy jumps and delays. The main aim of this paper is to investigate the effects of time delays and impulse stochastic interference on dynamics of the predator-prey model. First, we prove some properties of the subsystem of the system. Second, in view of comparison theorem and limit superior theory, we obtain the sufficient conditions for the extinction of this system. Furthermore, persistence in mean of the system is also investigated by using the theory of impulsive stochastic differential equations (ISDE) and delay differential equations (DDE). Finally, we carry out some simulations to verify our main results and explain the biological implications.
Investigation of the Scanning Microarc Oxidation Process
Authors: Xia Lingqin , Han Jianmin , Domblesky Joseph P. , Yang Zhiyong , Li Weijing
Published: June 2017

Scanning microarc oxidation (SMAO) is a coating process which is based on conventional microarc oxidation (MAO). The key difference is that deposition in SMAO is achieved by using a stainless steel nozzle to spray an electrolyte stream on the substrate surface as opposed to immersing the workpiece in an electrolyzer. In the present study, SMAO discharge characteristics, coating morphology, and properties are analyzed and compared to results obtained from MAO under similar conditions. Results show that MAO and SMAO have comparable spark and microarc lifetimes and sizes, though significant differences in incubation time and discharge distribution were evident. Results also showed that the voltage and current density for MAO and SMAO demonstrate similar behavior but have markedly different transient and steady-state values. Results obtained from coating A356 aluminum sheet show that oxide thickness and growth rate in SMAO are strongly dependent on interelectrode spacing and travel speed. Analysis of the SMAO coating morphology and structure showed that a denser and slightly harder layer was deposited in comparison to MAO and is attributed to reduced porosity and increased formation of α-Al2O3. Preliminary results indicate that SMAO represents a viable process for coating of aluminum surfaces.
Design and Analysis of Self-Healing Tree-Based Hybrid Spectral Amplitude Coding OCDMA System
Authors: Imtiaz Waqas A. , Qamar Affaq , Rehman Atiq Ur , Ali Haider , Chaudhry Adnan Rashid , Iqbal Javed
Published: June 2017

This paper presents an efficient tree-based hybrid spectral amplitude coding optical code division multiple access (SAC-OCDMA) system that is able to provide high capacity transmission along with fault detection and restoration throughout the passive optical network (PON). Enhanced multidiagonal (EMD) code is adapted to elevate system’s performance, which negates multiple access interference and associated phase induced intensity noise through efficient two-matrix structure. Moreover, system connection availability is enhanced through an efficient protection architecture with tree and star-ring topology at the feeder and distribution level, respectively. The proposed hybrid architecture aims to provide seamless transmission of information at minimum cost. Mathematical model based on Gaussian approximation is developed to analyze performance of the proposed setup, followed by simulation analysis for validation. It is observed that the proposed system supports 64 subscribers, operating at the data rates of 2.5 Gbps and above. Moreover, survivability and cost analysis in comparison with existing schemes show that the proposed tree-based hybrid SAC-OCDMA system provides the required redundancy at minimum cost of infrastructure and operation.
Effect of Oregano and Marjoram Essential Oils on the Physical and Antimicrobial Properties of Chitosan Based Systems
Authors: Sedlaříková Jana , Doležalová Magda , Egner Pavlína , Pavlačková Jana , Krejčí Jiří , Rudolf Ondřej , Peer Petra
Published: June 2017

The effect of two essential oils (EOs), from Origanum vulgare and Origanum majorana, their structural properties, and concentration on physical and antimicrobial characteristics of chitosan based solutions as well as films was investigated. Results showed that significantly different behaviour was induced by variation in the compositions of given essential oils. Film-forming solutions (FFS) containing oregano oil comprised considerably greater particles in comparison with the marjoram samples. Similarly, structural changes were confirmed by SEM analysis of chitosan films modified with the EOs; the smaller particles of the marjoram oil demonstrated better compatibility with chitosan matrix. However, chitosan films enriched with the oregano oil showed significantly superior antimicrobial activity compared to the marjoram. The dissimilar effects of the two EOs were also observed by water vapour pressure (WVP) measurement; increasing the amount of oregano oil triggered a drop in the WVP of the prepared films, whereas the marjoram oil had a negligible impact in this respect. These results suggest that the structural features of active substances in the EOs play a crucial role in determining the final properties of FFS and biofilm systems.
The Characteristic Properties of the Minimal Lp-Mean Width
Authors: Ma Tongyi
Published: June 2017

Giannopoulos proved that a smooth convex body K has minimal mean width position if and only if the measure hK(u)σ(du), supported on Sn-1, is isotropic. Further, Yuan and Leng extended the minimal mean width to the minimal Lp-mean width and characterized the minimal position of convex bodies in terms of isotropicity of a suitable measure. In this paper, we study the minimal Lp-mean width of convex bodies and prove the existence and uniqueness of the minimal Lp-mean width in its SL(n) images. In addition, we establish a characterization of the minimal Lp-mean width, conclude the average Mp(K) with a variation of the minimal Lp-mean width position, and give the condition for the minimum position of Mp(K).
Incidental Thrombus in Transit Causing Embolic Stroke
Authors: Malm Brian , Hermany Paul , Morrison Alan
Published: June 2017

Thrombus in transit leading to paradoxical systemic arterial embolism is a rare echocardiographic finding in patients presenting with embolic stroke. We present a case of a patient who had an atrial thrombus in transit discovered incidentally and later suffered a fatal stroke. Etiologies of cardioembolic stroke and the use of echocardiography in diagnosis and management are briefly discussed.
Multivariant Crystallization of Tetraplatin Precursors from Solutions Containing 1,2-C6H10(NH3)2 2+ and [PtCl6]2– Ions
Authors: Mulagaleev R. F. , Leshok D. Y. , Starkov A. K. , Matsulev A. N. , Kirik S. D.
Published: June 2017

Seven new phases containing hexachloroplatinate [PtCl6]2− and trans-1,2-dl-diammoniumcyclohexane 1,2-C6H10NH322+ ions were obtained by crystallization from solutions with minor variation of synthesis conditions. The compounds can be applied as precursors for the synthesis of effective anticancer drug tetraplatin ([PtC6H10(NH2)2Cl4]). The phase diversity was achieved by alterations including solvent acidity, crystallization rate, temperature, type of solvent, and the reagents ratio. The compounds were characterized by chemical and thermal analysis, IR, and 1H NMR spectroscopy. Crystal structures of the five compounds were determined by X-ray powder diffraction technique. The phases have ionic structures involving H2O, HCl molecules, or Cl− ions as supplementary species in the lattices. It helps to arrange some frames additionally interconnected by hydrogen bonds between ions and solvent molecules. It was suggested that crystal lattices adapted associated particles presented in solutions. It results in observed variety of the crystal structures. Besides the basic interest the obtained results are important for tetraplatin synthesis control.
Moringa oleifera Seeds Attenuate Vascular Oxidative and Nitrosative Stresses in Spontaneously Hypertensive Rats
Authors: Randriamboavonjy Joseph Iharinjaka , Rio Marc , Pacaud Pierre , Loirand Gervaise , Tesse Angela
Published: June 2017

Moringa oleifera (MOI) is a tree currently used in traditional medicine in tropical Africa, America, and Asia for therapeutic applications in several disorders including arterial hypertension. We previously described a cardiac protective role of a treatment with MOI seeds in spontaneously hypertensive rats (SHR). Here, we investigated the effects of this treatment on oxidative and nitrosative vascular stresses in SHR, with normotensive Wistar Kyoto rats used as controls. Oxidative and nitrosative stresses detected in SHR aortas using the fluorescent dye dihydroethidine and protein nitrotyrosine staining were reduced in MOI‐treated SHR aortas. This was associated with a decrease of free 8‐isoprostane circulating level, vascular p22phox and p47phox expressions, and SOD2 upregulation. Moreover, circulating nitrites and C‐reactive protein, increased in SHR, were both reduced in SHR receiving MOI. This was associated to decrease iNOS and NF‐κB protein expressions after MOI treatment. In functional studies, the endothelium‐dependent carbachol‐induced relaxation was improved in MOI‐treated SHR resistance arteries. Oral administration of MOI seeds demonstrates vascular antioxidant, anti‐inflammatory, and endothelial protective effects in SHR. Our data support the use of MOI seeds in diet against cardiovascular disorders associated with oxidative stress and inflammation such as hypertension, scientifically validating the use of these seeds in Malagasy traditional medicine.
Increased Serum Uric Acid Level Is a Risk Factor for Left Ventricular Hypertrophy but Not Independent of eGFR in Patients with Type 2 Diabetic Kidney Disease
Authors: Zeng Chuchu , Cheng Dongsheng , Sheng Xiaohua , Jian Guihua , Fan Ying , Chen Yuqiang , Li Junhui , Bao Hongda , Wang Niansong
Published: June 2017

Background.Although the relation between serum uric acid (SUA) and left ventricular hypertrophy (LVH) has been studied for decades, however, their association remains debatable.Methods.This is a retrospective study in which a total of 435 hospitalized Chinese patients with type 2 DKD were enrolled. The subjects were stratified into quartiles according to SUA level. LVH was assessed by two-dimensional guided M-mode echocardiography.Results.There was a significant increase in the prevalence of LVH in patients with type 2 DKD across SUA quartiles (28.9, 26.5, 36.1, and 49.5%;p<0.001). The Spearman analysis indicated that SUA was positively correlated to LVMI and negatively correlated to eGFR. The logistic regression analysis revealed that the odd ratio for LVH in the highest SUA quartile was 2.439 (95% CI 1.265–4.699;p=0.008; model 1) or 2.576 (95% CI 1.150–5.768;p=0.021; model 2) compared with that in the lowest SUA quartile. However, there was no significant increased risk of LVH in the subjects with the highest SUA quartile after adjusting the eGFR (OR = 1.750; 95% CI 0.685–4.470;p=0.242; model 3).Conclusions.In selected population, such as type 2 DKD, the elevated SUA level is positively linked with the increased risk of LVH, but this relationship is not independent of eGFR.