bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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

ABSTRACT

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

ABSTRACT

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

ABSTRACTIn 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

ABSTRACT

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

ABSTRACT

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

ObjectiveTo 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.MethodsA 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.ResultsOf 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.ConclusionsIn 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.
Glucose Catabolism in Liver Tumors Induced by c-MYC Can Be Sustained by Various PKM1/PKM2 Ratios and Pyruvate Kinase Activities
Authors: Méndez-Lucas Andrés , Li Xiaolei , Hu Junjie , Che Li , Song Xinhua , Jia Jiaoyuan , Wang Jingxiao , Xie Chencheng , Driscoll Paul C. , Tschaharganeh Darjus F. , Calvisi Diego F. , Yuneva Mariia , Chen Xin 
Published: June 2017

Abstract
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Because of differential regulation of enzymatic activities, PKM2, but not PKM1, has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL. Depletion of PKM2 at the time of c-MYC overexpression in murine livers did not affect c-MYC–induced tumorigenesis and resulted in liver tumor formation with decreased pyruvate kinase activity and decreased catabolism of glucose into alanine and the Krebs cycle. An increased PKM1/PKM2 ratio by ectopic PKM1 expression further decreased glucose flux into serine biosynthesis and increased flux into lactate and the Krebs cycle, resulting in reduced total levels of serine. However, these changes also did not affect c-MYC–induced liver tumor development. These results suggest that increased expression of PKM2 is not required to support c-MYC–induced tumorigenesis in the liver and that various PKM1/PKM2 ratios and pyruvate kinase activities can sustain glucose catabolism required for this process. Cancer Res; 77(16); 4355–64. ©2017 AACR.
Patient-Specific Drug Screening Using a Human Induced Pluripotent Stem Cell Model of Catecholaminergic Polymorphic Ventricular Tachycardia Type 2
Authors: Maizels Leonid , Huber Irit , Arbel Gil , Tijsen Anke J. , Gepstein Amira , Khoury Asaad , Gepstein Lior 
Published: June 2017

Background—

Catecholaminergic polymorphic ventricular tachycardia type 2 (CPVT2) results from autosomal recessive
CASQ2
mutations, causing abnormal Ca
2+
-handling and malignant ventricular arrhythmias. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of CPVT2 and to use the generated hiPSC-derived cardiomyocytes to gain insights into patient-specific disease mechanism and pharmacotherapy.

Methods and Results—

hiPSC cardiomyocytes were derived from a CPVT2 patient (D307H-
CASQ2
mutation) and from healthy controls. Laser-confocal Ca
2+
and voltage imaging showed significant Ca
2+
-transient irregularities, marked arrhythmogenicity manifested by early afterdepolarizations and triggered arrhythmias, and reduced threshold for store overload–induced Ca
2+
-release events in the CPVT2-hiPSC cardiomyocytes when compared with healthy control cells. Pharmacological studies revealed the prevention of adrenergic-induced arrhythmias by β-blockers (propranolol and carvedilol), flecainide, and the neuronal sodium-channel blocker riluzole; a direct antiarrhythmic action of carvedilol (independent of its α/β-adrenergic blocking activity), flecainide, and riluzole; and suppression of abnormal Ca
2+
cycling by the ryanodine stabilizer JTV-519 and carvedilol. Mechanistic insights were gained on the different antiarrhythmic actions of the aforementioned drugs, with carvedilol and JTV-519 (but not flecainide or riluzole) acting primarily through sarcoplasmic reticulum stabilization. Finally, comparable outcomes were found between flecainide and labetalol antiarrhythmic effects in vitro and the clinical results in the same patient.

Conclusions—
These results demonstrate the ability of hiPSCs cardiomyocytes to recapitulate CPVT2 disease phenotype and drug response in the culture dish, to provide novel insights into disease and drug therapy mechanisms, and potentially to tailor patient-specific drug therapy.
A Synoptic Climatology of Northern Hemisphere, Cold Season Polar and Subtropical Jet Superposition Events
Authors: Christenson Croix E. , Martin Jonathan E. , Handlos Zachary J. 
Published: June 2017

AbstractNarrow, tropopause-level wind speed maxima known as jet streams or jets are among the most ubiquitous structural characteristics of Earth’s atmosphere. Two species, the polar and subtropical jets, can be observed on any given day. The polar jet is tied, via eddy momentum flux convergence associated with extratropical wave development, to the troposphere-deep baroclinicity of the midlatitudes, while the subtropical jet is tied, by angular momentum constraints, to the poleward edge of the tropical Hadley cell. As a consequence of their different origins, the polar and subtropical jets are separated by both latitude and elevation. However, there are times when these two usually separate features become vertically superposed to form a single, intense jet core designated as a jet superposition or superposed jet. An objective method for identifying tropopause-level jets is employed in the construction of 50-yr cold season (November–March) synoptic climatologies of the Northern Hemisphere polar jet, subtropical jet, and jet superpositions. The analysis demonstrates that while superposition events are relatively rare, there are clear geographical maxima. Superpositions are most frequent in the western Pacific from December through February, with a secondary peak in southern North America and along its eastern seaboard. Consistent with expectations, the spatiotemporal maxima in jet superpositions appear to be coincident with maxima in the polar and subtropical jets.
Impact of the Montreal Protocol on Antarctic Surface Mass Balance and Implications for Global Sea Level Rise
Authors: Previdi Michael , Polvani Lorenzo M. 
Published: June 2017

Abstract
The Montreal Protocol on Substances that Deplete the Ozone Layer, adopted in 1987, is an international treaty designed to protect the ozone layer by phasing out emissions of chlorofluorocarbons and other ozone-depleting substances (ODSs). A growing body of scientific evidence now suggests that the implementation of the Montreal Protocol will have significant effects on climate over the next several decades, both by enabling stratospheric ozone recovery and by decreasing atmospheric concentrations of ODSs, which are greenhouse gases. Here, using a state-of-the-art chemistry–climate model, the Community Earth System Model (Whole Atmosphere Community Climate Model) [CESM(WACCM)], it is shown that the Montreal Protocol, through its impact on atmospheric ODS concentrations, leads to a substantial decrease in Antarctic surface mass balance (SMB) over the period 2006–65 relative to a hypothetical “World Avoided” scenario in which the Montreal Protocol has not been implemented. This SMB decrease produces an additional 25 mm of global sea level rise (GSLR) by the year 2065 relative to the present day. It is found, however, that the additional GSLR resulting from the relative decrease in Antarctic SMB is more than offset by a reduction in ocean thermal expansion, leading to a net mitigation of future GSLR due to the Montreal Protocol.