bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome Shrinkage and Loss of Nutrient-Providing Potential in the Obligate Symbiont of the Primitive Termite Mastotermes darwiniensis
Authors: Sabree Zakee L. , Huang Charlie Ye , Arakawa Gaku , Tokuda Gaku , Lo Nathan , Watanabe Hirofumi , Moran Nancy A. 
Published: October 2011

ABSTRACT

Beneficial microbial associations with insects are common and are classified as either one or a few intracellular species that are vertically transmitted and reside intracellularly within specialized organs or as microbial assemblages in the gut. Cockroaches and termites maintain at least one if not both beneficial associations.
Blattabacterium
is a flavobacterial endosymbiont of nearly all cockroaches and the termite
Mastotermes darwiniensis
and can use nitrogenous wastes in essential amino acid and vitamin biosynthesis. Key changes during the evolutionary divergence of termites from cockroaches are loss of
Blattabacterium
, diet shift to wood, acquisition of a specialized hindgut microbiota, and establishment of advanced social behavior. Termite gut microbes collaborate to fix nitrogen, degrade lignocellulose, and produce nutrients, and the absence of
Blattabacterium
in nearly all termites suggests that its nutrient-provisioning role has been replaced by gut microbes.
M. darwiniensis
is a basal, extant termite that solely retains
Blattabacterium
, which would show evidence of relaxed selection if it is being supplanted by the gut microbiome. This termite-associated
Blattabacterium
genome is ∼8% smaller than cockroach-associated
Blattabacterium
genomes and lacks genes underlying vitamin and essential amino acid biosynthesis. Furthermore, the
M. darwiniensis
gut microbiome membership is more consistent between individuals and includes specialized termite gut-associated bacteria, unlike the more variable membership of cockroach gut microbiomes. The
M. darwiniensis Blattabacterium
genome may reflect relaxed selection for some of its encoded functions, and the loss of this endosymbiont in all remaining termite genera may result from its replacement by a functionally complementary gut microbiota.
Fecal Indicators and Zoonotic Pathogens in Household Drinking Water Taps Fed from Rainwater Tanks in Southeast Queensland, Australia
Authors: Ahmed W. , Hodgers L. , Sidhu J. P. S. , Toze S. 
Published: October 2011

ABSTRACT

In this study, the microbiological quality of household tap water samples fed from rainwater tanks was assessed by monitoring the numbers of
Escherichia coli
bacteria and enterococci from 24 households in Southeast Queensland (SEQ), Australia. Quantitative PCR (qPCR) was also used for the quantitative detection of zoonotic pathogens in water samples from rainwater tanks and connected household taps. The numbers of zoonotic pathogens were also estimated in fecal samples from possums and various species of birds by using qPCR, as possums and birds are considered to be the potential sources of fecal contamination in roof-harvested rainwater (RHRW). Among the 24 households, 63% of rainwater tank and 58% of connected household tap water (CHTW) samples contained
E. coli
and exceeded Australian drinking water guidelines of <1 CFU
E. coli
per 100 ml water. Similarly, 92% of rainwater tanks and 83% of CHTW samples also contained enterococci. In all, 21%, 4%, and 13% of rainwater tank samples contained
Campylobacter
spp.,
Salmonella
spp., and
Giardia lamblia
, respectively. Similarly, 21% of rainwater tank and 13% of CHTW samples contained
Campylobacter
spp. and
G. lamblia
, respectively. The number of
E. coli
(
P
= 0.78),
Enterococcus
(
P
= 0.64),
Campylobacter
(
P
= 0.44), and
G. lamblia
(
P
= 0.50) cells in rainwater tanks did not differ significantly from the numbers observed in the CHTW samples. Among the 40 possum fecal samples tested,
Campylobacter
spp.,
Cryptosporidium parvum
, and
G. lamblia
were detected in 60%, 13%, and 30% of samples, respectively. Among the 38 bird fecal samples tested,
Campylobacter
spp.,
Salmonella
spp.,
C. parvum
, and
G. lamblia
were detected in 24%, 11%, 5%, and 13% of the samples, respectively. Household tap water samples fed from rainwater tanks tested in the study appeared to be highly variable. Regular cleaning of roofs and gutters, along with pruning of overhanging tree branches, might also prove effective in reducing animal fecal contamination of rainwater tanks.
SPM1 Stabilizes Subpellicular Microtubules in Toxoplasma gondii
Authors: Tran Johnson Q. , Li Catherine , Chyan Alice , Chung Lawton , Morrissette Naomi S. 
Published: October 2011

ABSTRACTWe have identified two novel proteins that colocalize with thesubpellicularmicrotubules in the protozoan parasiteToxoplasma gondiiand named these proteins SPM1 and SPM2. These proteins have basic isoelectric points and both have homologs in other apicomplexan parasites. SPM1 contains six tandem copies of a 32-amino-acid repeat, whereas SPM2 lacks defined protein signatures. Alignment ofToxoplasmaSPM2 with apparentPlasmodiumSPM2 homologs indicates that the greatest degree of conservation lies in the carboxy-terminal half of the protein. Analysis ofPlasmodiumhomologs of SPM1 indicates that while the central 32-amino-acid repeats have expanded to different degrees (7, 8, 9, 12, or 13 repeats), the amino- and carboxy-terminal regions remain conserved. In contrast, although theCryptosporidiumSPM1 homolog has a conserved carboxy tail, the five repeats are considerably diverged, and it has a smaller amino-terminal domain. SPM1 is localized along the full length of the subpellicular microtubules but does not associate with the conoid or spindle microtubules. SPM2 has a restricted localization along the middle region of the subpellicular microtubules. Domain deletion analysis indicates that four or more copies of the SPM1 repeat are required for localization to microtubules, and the amino-terminal 63 residues of SPM2 are required for localization to the subpellicular microtubules. Gene deletion studies indicate that neither SPM1 nor SPM2 is essential for tachyzoite viability. However, loss of SPM1 decreases overall parasite fitness and eliminates the stability of subpellicular microtubules to detergent extraction.
Ultrastructure of the Denitrifying Methanotroph “Candidatus Methylomirabilis oxyfera,” a Novel Polygon-Shaped Bacterium
Authors: Wu Ming L. , van Teeseling Muriel C. F. , Willems Marieke J. R. , van Donselaar Elly G. , Klingl Andreas , Rachel Reinhard , Geerts Willie J. C. , Jetten Mike S. M. , Strous Marc , van Niftrik Laura 
Published: October 2011

ABSTRACT

“
Candidatus
Methylomirabilis oxyfera” is a newly discovered denitrifying methanotroph that is unrelated to previously known methanotrophs. This bacterium is a member of the NC10 phylum and couples methane oxidation to denitrification through a newly discovered intra-aerobic pathway. In the present study, we report the first ultrastructural study of “
Ca
. Methylomirabilis oxyfera” using scanning electron microscopy, transmission electron microscopy, and electron tomography in combination with different sample preparation methods. We observed that “
Ca
. Methylomirabilis oxyfera” cells possess an atypical polygonal shape that is distinct from other bacterial shapes described so far. Also, an additional layer was observed as the outermost sheath, which might represent a (glyco)protein surface layer. Further, intracytoplasmic membranes, which are a common feature among proteobacterial methanotrophs, were never observed under the current growth conditions. Our results indicate that “
Ca
. Methylomirabilis oxyfera” is ultrastructurally distinct from other bacteria by its atypical cell shape and from the classical proteobacterial methanotrophs by its apparent lack of intracytoplasmic membranes.
Homodimerization and Binding of Specific Domains to the Target DNA Are Essential Requirements for HlyU To Regulate Expression of the Virulence Gene
rtxA1
, Encoding the Repeat-in-Toxin Protein in the Human Pathogen Vibrio vulnificus
Authors: Liu Moqing , Rose Michael , Crosa Jorge H. 
Published: October 2011

ABSTRACT

The virulence gene
rtxA1
, encoding the repeat-in-toxin protein, plays an essential role in the pathogenesis of
Vibrio vulnificus
infections. Expression of this gene is controlled by the HlyU regulator by direct contact of the DNA upstream of the
rtxA1
toxin operon acting as a derepressor of the H-NS protein. The crystal structure suggests that HlyU forms a homodimer
in vitro
. However, knowledge of the biological implications of these findings
in vivo
is limited. In this work, we endeavored to dissect, using genetic and biochemical approaches, the domains of this protein that are essential for homodimer formation and the interaction of HlyU with the target DNA. We identified that residues L18, N22, R25, S54, Q55, L57, W59, R61, K70, and Y77 are essential for the HlyU protein binding to the DNA and that amino acids L17 and L91 are important for HlyU dimerization. We also determined that HlyU homodimer formation is an essential requirement for binding to the upstream region of the
rtxA1
operon and is the key feature in relieving the H-NS repression of
rtxA1
transcription.
Role of Secondary Transporters and Phosphotransferase Systems in Glucose Transport by Oenococcus oeni
Authors: Kim Ok Bin , Richter Hanno , Zaunmüller Tanja , Graf Sabrina , Unden Gottfried 
Published: October 2011

ABSTRACTGlucose uptake by the heterofermentative lactic acid bacteriumOenococcus oeniB1 was studied at the physiological and gene expression levels. Glucose- or fructose-grown bacteria catalyzed uptake of [14C]glucose over a pH range from pH 4 to 9, with maxima at pHs 5.5 and 7. Uptake occurred in two-step kinetics in a high- and low-affinity reaction. The high-affinity uptake followed Michaelis-Menten kinetics and required energization. It accumulated the radioactivity of glucose by a factor of 55 within the bacteria. A large portion (about 80%) of the uptake of glucose was inhibited by protonophores and ionophores. Uptake of the glucose at neutral pH was not sensitive to degradation of the proton potential, Δp. Expression of the genes OEOE_0819 and OEOE_1574 (here referred to as 0819 and 1574), coding for secondary transporters, was induced by glucose as identified by quantitative real-time (RT)-PCR. The genes 1574 and 0819 were able to complement growth of aBacillus subtilishexose transport-deficient mutant on glucose but not on fructose. The genes 1574 and 0819 therefore encode secondary transporters for glucose, and the transports are presumably Δpdependent.O. oenicodes, in addition, for a phosphotransferase transport system (PTS) (gene OEOE_0464 [0464] for the permease) with similarity to the fructose- and mannose-specific PTS of lactic acid bacteria. Quantitative RT-PCR showed induction of the gene 0464 by glucose and by fructose. The data suggest that the PTS is responsible for Δp-independent hexose transport at neutral pH and for the residual Δp-independent transport of hexoses at acidic pH.
Cost-effectiveness of cardiac resynchronisation therapy for patients with moderate-to-severe heart failure: a lifetime Markov model
Authors: Neyt Mattias , Stroobandt Serge , Obyn Caroline , Camberlin Cécile , Devriese Stephan , De Laet Chris , Van Brabandt Hans 
Published: October 2011

ObjectiveTo assess the cost-effectiveness of cardiac resynchronisation therapy (CRT) both with CRT-P (biventricular pacemaker only) and with CRT-D (biventricular pacemaker with defibrillator) in patients with New York Heart Association (NYHA) functional class III/IV from a Belgian healthcare-payer perspective.MethodsA lifetime Markov model was designed to calculate the cost–utility of both interventions. In the reference case, the treatment effect was based on the Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure trial. Costs were based on real-world data. Pharmacoeconomic guidelines were applied, including probabilistic modelling and sensitivity analyses.ResultsCompared with optimal medical treatment, on average 1.31 quality-adjusted life-years (QALY) are gained with CRT-P at an additional cost of €14 700, resulting in an incremental cost-effectiveness ratio (ICER) of about €364;11 200/QALY. As compared with CRT-P, CRT-D treatment adds on average an additional 0.55 QALYs at an extra cost of €30 900 resulting in an ICER of €57 000/QALY. This result was very sensitive to the incremental clinical benefit of the defibrillator function on top of CRT.ConclusionsBased on efficiency arguments, CRT-P can be recommended for NYHA class III and IV patients if there is a willingness to pay more than €11 000/QALY. Even though CRT-D may offer a survival benefit over CRT-P, the incremental clinical benefit appears to be too marginal to warrant a threefold-higher device price for CRT-D. Further clinical research should focus on the added value of CRT-D over CRT-P.
Molecular Pathways: Targeting Proteasomal Protein Degradation in Cancer
Authors: Molineaux Susan M. 
Published: October 2011

Abstract
With the approval by the U.S. Food and Drug Administration of bortezomib for the treatment of multiple myeloma and mantle cell lymphoma, the proteasome was clinically validated as a target in oncology. The proteasome is part of a complex cellular pathway that controls the specificity and rate of degradation of the majority of proteins in the cell. The search for additional drug targets in the proteasomal pathway is ongoing. In parallel, the next generation of proteasome inhibitors, exhibiting some properties distinct from that of bortezomib, are currently being studied in clinical trials. The key question will be whether these distinctions can improve upon the clinical efficacy and safety standards established by bortezomib and refine our understanding of the mechanism by which proteasome inhibitors are effective in the treatment of cancer. Clin Cancer Res; 18(1); 15–20. ©2011 AACR.
Lysophosphatidic Acid Signaling Protects Pulmonary Vasculature From Hypoxia-Induced Remodeling
Authors: Cheng Hsin-Yuan , Dong Anping , Panchatcharam Manikandan , Mueller Paul , Yang Fanmuyi , Li Zhenyu , Mills Gordon , Chun Jerold , Morris Andrew J. , Smyth Susan S. 
Published: October 2011

Objective—
Lysophosphatidic acid (LPA) is a bioactive lipid molecule produced by the plasma lysophospholipase D enzyme autotaxin that is present at ≥100 nmol/L in plasma. Local administration of LPA promotes systemic arterial remodeling in rodents. To determine whether LPA contributes to remodeling of the pulmonary vasculature, we examined responses in mice with alterations in LPA signaling and metabolism.

Methods and Results—

Enpp2
+/−
mice, which are heterozygous for the autotaxin-encoding gene and which have reduced expression of autotaxin/lysophospholipase D and approximately half normal plasma LPA, were hyperresponsive to hypoxia-induced vasoconstriction and remodeling, as evidenced by the development of higher right ventricular (RV) systolic pressure, greater decline in peak flow velocity across the pulmonary valve, and a higher percentage of muscularized arterioles. Mice lacking LPA
1
and LPA
2
, 2 LPA receptors abundantly expressed in the vasculature, also had enhanced hypoxia-induced pulmonary remodeling. With age,
Lpar1
−/−
2
−/−
mice spontaneously developed elevated RV systolic pressure and RV hypertrophy that was not observed in
Lpar1
−/−
mice or
Lpar2
−/−
mice. Expression of endothelin-1, a potent vasoconstrictor, was elevated in lungs of
Lpar1
−/−
2
−/−
mice, and expression of endothelin
B
receptor, which promotes vasodilation and clears endothelin, was reduced in
Enpp2
+/−
and
Lpar1
−/−
2
−/−
mice.

Conclusion—

Our findings indicate that LPA may negatively regulate pulmonary vascular pressure through LPA
1
and LPA
2
receptors and that in the absence of LPA signaling, upregulation in the endothelin system favors remodeling.
Overexpression of Tissue Inhibitor of Metalloproteinase 3 in Macrophages Reduces Atherosclerosis in Low-Density Lipoprotein Receptor Knockout Mice
Authors: Casagrande Viviana , Menghini Rossella , Menini Stefano , Marino Arianna , Marchetti Valentina , Cavalera Michele , Fabrizi Marta , Hribal Marta L. , Pugliese Giuseppe , Gentileschi Paolo , Schillaci Orazio , Porzio Ottavia , Lauro Davide , Sbraccia Paolo , Lauro Renato , Federici Massimo 
Published: October 2011

Objective—

Tissue inhibitor of metalloproteinase 3 (TIMP3) is a stromal protein that inhibits the activity of proteases and receptors. TIMP3 is downregulated in metabolic and inflammatory disorders, such as type 2 diabetes mellitus and atherosclerosis, particularly in regions enriched with monocyte/macrophage cells. To investigate the role of TIMP3 in atherosclerosis, we generated a new mouse model in which
Timp3
was overexpressed in the atherosclerotic plaque via a macrophage-specific promoter (MacT3). We elucidated any potential antiatherosclerotic effects of TIMP3, including regulation of monocyte/macrophage recruitment within atherosclerotic plaques, in MacT3 mice crossbred with low-density lipoprotein receptor knockout (LDLR
−/−
) mice.

Methods and Results—

MacT3/LDLR
−/−
mice had an improvement of atherosclerosis and metabolic parameters compared with LDLR
−/−
.
En face
aorta and aortic root examination of MacT3/LDLR
−/−
mice revealed smaller atherosclerotic plaques with features of stability, such as increased collagen content and decreased necrotic core formation. Atherosclerotic plaques in MacT3/LDLR
−/−
mice contained fewer T cells and macrophages. Furthermore, TIMP3 overexpression in macrophages resulted in reduced oxidative stress signals, as evidenced by lower lipid peroxidation, protein carbonylation, and nitration in atheromas.

Conclusion—
Our study confirmed that macrophage-specific overexpression of TIMP3 decreases the inflammatory content and the amplitude of atherosclerotic plaques in mice.
Disruption of Endothelial Peroxisome Proliferator-Activated Receptor γ Accelerates Diet-Induced Atherogenesis in LDL Receptor-Null Mice
Authors: Qu Aijuan , Shah Yatrik M. , Manna Soumen K. , Gonzalez Frank J. 
Published: October 2011

Objective—
Peroxisome proliferator-activated receptor γ (PPARγ) is widely expressed in vessel walls, and it's activation by agonists showed beneficial effects in cardiovascular diseases. However, the role of endothelial cell (EC) PPARγ in atherogenesis is not fully understood.

Methods and Results—

To assess the contribution of endothelial-specific PPARγ in atherosclerosis, EC-specific PPARγ disruption and LDL receptor (LDLR) double-knockout (PPARγ
ΔEC
/LDLR
−/−
) mice were developed. When challenged with a high-cholesterol diet for 4 weeks, PPARγ
ΔEC
/LDLR
−/−
mice exhibited severe atherosclerotic lesions compared to either their littermate controls or macrophage-specific PPARγ disruption and LDLR double knockout (PPARγ
ΔMΦ
/LDLR
−/−
) mice. Metabolic analysis showed severe dyslipidemia and significant increase in systolic blood pressure in the PPARγ
ΔEC
/LDLR
−/−
mice. Histological analysis and real-time quantitative PCR suggested an exacerbated inflammation in PPARγ
ΔEC
/LDLR
−/−
mice, as revealed by the increases of proinflammatory gene expression and macrophage infiltration in vivo and in vitro. Furthermore, in vivo endothelial permeability was also increased by endothelial PPARγ disruption. Bone-marrow transplantation studies, which reconstituted hematopoietic PPARγ, demonstrated that the accelerated atherogenesis was due to endothelial PPARγ deficiency.

Conclusion—
Endothelial PPARγ plays an important protective role in atherogenesis.
Moyamoya Disease in China
Authors: Duan Lian , Bao Xiang-Yang , Yang Wei-Zhong , Shi Wan-Chao , Li De-Sheng , Zhang Zheng-Shan , Zong Rui , Han Cong , Zhao Feng , Feng Jie 
Published: October 2011

Background and Purpose—
Here we describe the clinical features and outcomes of patients with moyamoya disease who were surgically treated at a single institution in China.

Methods—
Our cohort included 802 patients with moyamoya disease. Demographic and clinical characteristics were obtained by retrospective chart review; follow-up information and outcome were obtained through clinical visits, telephone, or letter interview. We used the Kaplan-Meier methods to estimate stroke risk by treatment status.

Results—
The median age for the onset of symptoms was 28 (range, 0.5–77) years. Two definite peaks in age distribution were found. The ratio of women to men was 1:1 (398/404). Familial occurrence of moyamoya disease was 5.2%. The initial symptom was ischemia, hemorrhage, or others in 564, 113, and 125 patients, respectively. Twenty-nine of the 802 patients (3.6%) received conservative management. The remaining 773 patients (96.4%) underwent neurosurgical revascularization procedures, and 502 of these were bilateral. The median follow-up after surgery (n=773) or conservative management (n=26) was 26.3 months (range, 6.0–101.9 months). Most subsequent ischemic events appeared in the first 2 years after surgery. The Kaplan-Meier estimated stroke risk was 10.1% in the first 2 years, and the 5-year-Kaplan-Meier risk of stroke was 12.7% after surgery for all patients treated with surgical revascularization.

Conclusions—
This study on the clinical features of moyamoya disease in mainland China indicated bimodal incidence distribution with women-to-men ratios of 1:1 and lower rate of hemorrhages in adults compared with in children. Patients had low rates of postoperative ischemic or hemorrhagic strokes, and the majority of patients had preserved functional status after revascularization.
Successful Regeneration After Experimental Stroke by Granulocyte-Colony Stimulating Factor Is Not Further Enhanced by Constraint-Induced Movement Therapy Either in Concurrent or in Sequential Combination Therapy
Authors: Diederich Kai , Quennet Verena , Bauer Henrike , Müller Harald D. , Wersching Heike , Schäbitz Wolf-Rüdiger , Minnerup Jens , Sommer Clemens 
Published: October 2011

Background and Purpose—
Both application of granulocyte-colony stimulating factor (G-CSF) and constraint-induced movement therapy (CIMT) have been shown to improve outcome after experimental stroke. The aim of the present study was to determine whether concurrent or sequential combination of both therapies will further enhance therapeutic benefit and whether specific modifications in the abundance of various neurotransmitter receptors do occur.

Methods—

Adult male Wistar rats were subjected to photothrombotic ischemia and assigned to the following treatment groups (n=20 each): (1) ischemic control (saline); (2) CIMT (CIMT between poststroke Days 2 and 11; (3) G-CSF (10 μg/kg G-CSF daily between poststroke Days 2 and 11; (4) combined concurrent group (CIMT plus 10 μg/kg G-CSF daily between poststroke Days 2 and 11; and (5) combined sequential group (CIMT between poststroke Days 2 and 11 and 10 μg/kg G-CSF daily between poststroke Days 12 and 21, respectively). Rats were functionally tested before and up to 4 weeks after ischemia. Quantitative receptor autography was performed for
N
-methyl-
d
-aspartate, AMPA, and GABA
A
receptors.

Results—
Significant improvement of functional outcome was seen in all groups treated with G-CSF alone and in either combination with CIMT, whereas CIMT alone failed to enhance recovery. Infarct sizes and remaining cortical tissue did not differ in the various treatment groups. Failure of significant benefit in the CIMT group was associated with a shift toward inhibition in perilesional and remote cortical regions.

Conclusions—
Our findings disclose G-CSF as the major player for enhanced recovery after experimental stroke, preventing a shift toward inhibition as seen in the CIMT group.