bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soluble urokinase plasminogen activator receptor, C‐reactive protein and triglyceride are associated with heart rate variability in non‐diabetic Danes
Authors: Intzilakis Theodoros , Hartmann Gro , Mouridsen Mette R. , Eugen‐Olsen Jesper , Kumarathurai Preman , Madsbad Sten , Almdal Thomas P. , Haugaard Steen B. , Sajadieh Ahmed 
Published: February 2013

AbstractBackgroundHeart rate variability (HRV) is associated with an increased risk of cardiovascular morbidity and mortality. HRV is in part a function of the activity of the autonomic nervous system and has been associated with low‐grade inflammation. In patients with type 2 diabetes, HRV is decreased and is a predictor of poor outcome. As HRV and its determinants in non‐diabetic individuals have not been studied properly, the aim of this observational study was to evaluate possible associations between HRV vs. impaired fasting glucose, insulin resistance, lipidaemia and markers of inflammation and immune activation in these individuals.Materials and methodsHealthy individuals (n = 596, 55–75 years) from the community were evaluated with ambulant 48‐h continuous electrocardiogram monitoring and fasting markers of lipidaemia, inflammation and immune activation, respectively. Insulin resistance was estimated by HOMA‐IR. Time domain components of HRV were calculated.ResultsHeart rate and HRV were not associated with glucose metabolic parameters but were inversely associated with soluble urokinase plasminogen activator receptor (suPAR), high‐sensitive CRP and leucocyte number (P < 0·001), respectively. Both 24‐h and night‐time HRV were inversely associated with plasma triglyceride, whereas HDL, LDL and total cholesterol were not. A model including suPAR, CRP, gender, triglyceride, age, systolic blood pressure, physical activity and smoking status explained 12·2% (P < 0·0001) of the 24‐h HRV and 7·3% (P < 0·0001) of the night‐time HRV. The single strongest factor to explain 24‐h and night‐time HRV appeared to be suPAR (P = 0·001 and P = 0·0067, respectively).ConclusionA low HRV is not related to prediabetes, that is, insulin resistance and impaired fasting glucose, but is related to the immune and inflammatory markers suPAR and CRP and plasma triglyceride.
Genetic Examination of Initial Amino Acid Oxidation and Glutamate Catabolism in the Hyperthermophilic Archaeon Thermococcus kodakarensis
Authors: Yokooji Yuusuke , Sato Takaaki , Fujiwara Shinsuke , Imanaka Tadayuki , Atomi Haruyuki 
Published: February 2013

ABSTRACT

Amino acid catabolism in
Thermococcales
is presumed to proceed via three steps: oxidative deamination of amino acids by glutamate dehydrogenase (GDH) or aminotransferases, oxidative decarboxylation by 2-oxoacid:ferredoxin oxidoreductases (KOR), and hydrolysis of acyl-coenzyme A (CoA) by ADP-forming acyl-CoA synthetases (ACS). Here, we performed a genetic examination of enzymes involved in Glu catabolism in
Thermococcus kodakarensis
. Examination of amino acid dehydrogenase activities in cell extracts of
T. kodakarensis
KUW1 (Δ
pyrF
Δ
trpE
) revealed high NADP-dependent GDH activity, along with lower levels of NAD-dependent activity. NADP-dependent activities toward Gln/Ala/Val/Cys and an NAD-dependent threonine dehydrogenase activity were also detected. In KGDH1, a gene disruption strain of
T. kodakarensis
GDH (Tk-GDH), only threonine dehydrogenase activity was detected, indicating that all other activities were dependent on Tk-GDH. KGDH1 could not grow in a medium in which growth was dependent on amino acid catabolism, implying that Tk-GDH is the only enzyme that can discharge the electrons (to NADP
+
/NAD
+
) released from amino acids in their oxidation to 2-oxoacids. In a medium containing excess pyruvate, KGDH1 displayed normal growth, but higher degrees of amino acid catabolism were observed compared to those for KUW1, suggesting that Tk-GDH functions to suppress amino acid oxidation and plays an anabolic role under this condition. We further constructed disruption strains of 2-oxoglutarate:ferredoxin oxidoreductase and succinyl-CoA synthetase. The two strains displayed growth defects in both media compared to KUW1. Succinate generation was not observed in these strains, indicating that the two enzymes are solely responsible for Glu catabolism among the multiple KOR and ACS enzymes in
T. kodakarensis
.
PARI Overexpression Promotes Genomic Instability and Pancreatic Tumorigenesis
Authors: O'Connor Kevin W. , Dejsuphong Donniphat , Park Eunmi , Nicolae Claudia M. , Kimmelman Alec C. , D'Andrea Alan D. , Moldovan George-Lucian 
Published: February 2013

Abstract
Treatment options for patients with pancreatic ductal adenocarcinoma (PDAC) remain limited. Therapeutic targets of interest include mutated molecules that predispose to pancreatic cancer such as KRAS and TP53. Here, we show that an element of the homologous recombination pathway of DNA repair, the PARP-binding protein C12orf48/PARI (PARPBP), is overexpressed specifically in pancreatic cancer cells where it is an appealing candidate for targeted therapy. PARI upregulation in pancreatic cancer cells or avian DT40 cells conferred DNA repair deficiency and genomic instability. Significantly, PARI silencing compromised cancer cell proliferation in vitro, leading to cell-cycle alterations associated with S-phase delay, perturbed DNA replication, and activation of the DNA damage response pathway in the absence of DNA damage stimuli. Conversely, PARI overexpression produced tolerance to DNA damage by promoting replication of damaged DNA. In a mouse xenograft model of pancreatic cancer, PARI silencing was sufficient to reduce pancreatic tumor growth in vivo. Taken together, our findings offered a preclinical proof-of-concept for PARI as candidate therapeutic target to treat PDAC. Cancer Res; 73(8); 2529–39. ©2013 AACR.
Phylogenetic analysis of erythritol catabolic loci within theRhizobiales and Proteobacteria
Authors: Geddes Barney A , Hausner Georg , Oresnik Ivan J 
Published: February 2013

Abstract

Background
The ability to use erythritol as a sole carbon source is not universal amongthe Rhizobiaceae. Based on the relatedness to the catabolic genes inBrucella it has been suggested that the eryABCD operonmay have been horizontally transferred into Rhizobium. During workcharacterizing a locus necessary for the transport and catabolism oferythritol, adonitol and L-arabitol in Sinorhizobium meliloti, webecame interested in the differences between the erythritol loci of S.meliloti and R. leguminosarum. Utilizing the OrthologNeighborhood Viewer from the DOE Joint Genome Institute database it appearedthat loci for erythritol and polyol utilization had distinct arrangementsthat suggested these loci may have undergone genetic rearrangements.

Results
A data set was established of genetic loci containing erythritol/polyolorthologs for 19 different proteobacterial species. These loci were analyzedfor genetic content and arrangement of genes associated with erythritol,adonitol and L-arabitol catabolism. Phylogenetic trees were constructed forcore erythritol catabolic genes and contrasted with the species phylogeny.Additionally, phylogenetic trees were constructed for genes that showeddifferences in arrangement among the putative erythritol loci in thesespecies.

Conclusions
Three distinct erythritol/polyol loci arrangements have been identified thatreflect metabolic need or specialization. Comparison of the phylogenetictrees of core erythritol catabolic genes with species phylogeny providesevidence that is consistent with these loci having been horizontallytransferred from the alpha-proteobacteria into both the beta andgamma-proteobacteria. ABC transporters within these loci adopt 2 uniquegenetic arrangements, and although biological data suggests they arefunctional erythritol transporters, phylogenetic analysis suggests they maynot be orthologs and probably should be considered analogs. Finally,evidence for the presence of paralogs, and xenologs of erythritol catabolicgenes in some of the genomes included in the analysis is provided.
Angiotensin-converting enzyme inhibition and food restriction restore delayed preconditioning in diabetic mice
Authors: Van der Mieren Gerry , Nevelsteen Ines , Vanderper Annelies , Oosterlinck Wouter , Flameng Willem , Herijgers Paul 
Published: February 2013

Abstract

Background
Classical and delayed preconditioning are powerful endogenous protection mechanisms against ischemia-reperfusion damage. However, it is still uncertain whether delayed preconditioning can effectively salvage myocardium in patients with co-morbidities, such as diabetes and the metabolic syndrome. We investigated delayed preconditioning in mice models of type II diabetes and the metabolic syndrome and investigated interventions to optimize the preconditioning potential.

Methods
Hypoxic preconditioning was induced in C57Bl6-mice (WT), leptin deficient ob/ob (model for type II diabetes) and double knock-out (DKO) mice with combined leptin and LDL-receptor deficiency (model for metabolic syndrome). Twenty-four hours later, 30 min of regional ischemia was followed by 60 min reperfusion. Left ventricular contractility and infarct size were studied. The effect of 12 weeks food restriction or angiotensin-converting enzyme inhibition (ACE-I) on this was investigated. Differences between groups were analyzed for statistical significance by student’s t-test or one-way ANOVA followed by a Fisher’s LSD post hoc test. Factorial ANOVA was used to determine the interaction term between preconditioning and treatments, followed by a Fisher’s LSD post hoc test. Two-way ANOVA was used to determine the relationship between infarct size and contractility (PRSW). A value of p<0.05 was considered significant.

Results
Left ventricular contractility is reduced in ob/ob compared with WT and even further reduced in DKO. ACE-I improved contractility in ob/ob and DKO mice. After ischemia/reperfusion without preconditioning, infarct size was larger in DKO and ob/ob versus WT. Hypoxic preconditioning induced a strong protection in WT and a partial protection in ob/ob mice. The preconditioning potential was lost in DKO. Twelve weeks of food restriction or ACE-I restored the preconditioning potential in DKO and improved it in ob/ob.

Conclusion
Delayed preconditioning is restored by food restriction and ACE-I in case of type II diabetes and the metabolic syndrome.
Policy development, implementation and evaluation by the AIDS control program in Uganda: a review of the processes
Authors: Tumwesigye Benson T , Nakanjako Damalie , Wanyenze Rhoda , Akol Zainab , Sewankambo Nelson 
Published: February 2013

Abstract

Background
The AIDS Control Program (ACP) in Uganda has spearheaded the national health sector HIV response for the last three decades. ACP has developed, revised and implemented various HIV prevention, care and treatment policies in order to keep interventions relevant to the changing dynamics of the HIV epidemic. However, the ACP team and partners remain concerned about the lengthy policy development processes. This study documented the policy development and revision processes to identify strengths and weaknesses in order to inform adjustments as Uganda embraces the move to ‘zero’ HIV infections.

Methods
Data was collected through a review of the relevant policy documents and key informant interviews with the five program officers involved in the recently developed Safe Male Circumcision (SMC) policy and the recently revised HIV Counseling and Testing (HCT) policy. Qualitative data was analyzed manually using pre-determined themes.

Results
Development and revision of the SMC and HCT policies followed similar processes that included a series of meetings between senior management and a selected technical working group. However, the gaps included: i) inadequate awareness of the existence of national policy development and management guidelines; ii) limited engagement of the policy analysis unit in the policy development/revision processes; iii) inadequate tracking and evaluation of the policies before revision or development of new related policies; iv) lack of specific protocols/standard operating procedures (SOPs); and, v) limited indigenous funding for the entire policy development processes which contributed to non-adherence to the anticipated timelines.

Conclusions
Policy development and revision of the SMC and HCT policies followed similar processes. Gaps identified included lack of protocols/SOPs for the processes and limited indigenous funding to support adherence to anticipated timelines. We recommend active involvement of the policy analysis unit in all policy processes. Specific protocols/SOPs for development, analysis, revision, implementation, monitoring, evaluation and impact assessment processes should be developed prior to commencement of the activities.
Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure
Authors: Mesplède Thibault , Quashie Peter K , Osman Nathan , Han Yingshan , Singhroy Diane N , Lie Yolanda , Petropoulos Christos J , Huang Wei , Wainberg Mark A 
Published: February 2013

Abstract

Background
Clinical studies have shown that integrase strand transfer inhibitors can be used to treat HIV-1 infection. Although the first-generation integrase inhibitors are susceptible to the emergence of resistance mutations that impair their efficacy in therapy, such resistance has not been identified to date in drug-naïve patients who have been treated with the second-generation inhibitor dolutegravir. During previous in vitro selection study, we identified a R263K mutation as the most common substitution to arise in the presence of dolutegravir with H51Y arising as a secondary mutation. Additional experiments reported here provide a plausible explanation for the absence of reported dolutegravir resistance among integrase inhibitor-naïve patients to date.

Results
We now show that H51Y in combination with R263K increases resistance to dolutegravir but is accompanied by dramatic decreases in both enzymatic activity and viral replication.

Conclusions
Since H51Y and R263K may define a unique resistance pathway to dolutegravir, our results are consistent with the absence of resistance mutations in antiretroviral drug-naive patients treated with this drug.
Moderate excess of pyruvate augments osteoclastogenesis
Authors: Fong Jenna E. , Le Nihouannen Damien , Tiedemann Kerstin , Sadvakassova Gulzhakhan , Barralet Jake E. , Komarova Svetlana V. 
Published: February 2013

Summary
Cell differentiation leads to adaptive changes in energy metabolism. Conversely, hyperglycemia induces malfunction of many body systems, including bone, suggesting that energy metabolism reciprocally affects cell differentiation. We investigated how the differentiation of bone-resorbing osteoclasts, large polykaryons formed through fusion and growth of cells of monocytic origin, is affected by excess of energy substrate pyruvate and how energy metabolism changes during osteoclast differentiation. Surprisingly, small increases in pyruvate (1–2 mM above basal levels) augmented osteoclastogenesis in vitro and in vivo, while larger increases were not effective in vitro. Osteoclast differentiation increased cell mitochondrial activity and ATP levels, which were further augmented in energy-rich conditions. Conversely, the inhibition of respiration significantly reduced osteoclast number and size. AMP-activated protein kinase (AMPK) acts as a metabolic sensor, which is inhibited in energy-rich conditions. We found that osteoclast differentiation was associated with an increase in AMPK levels and a change in AMPK isoform composition. Increased osteoclast size induced by pyruvate (1 mM above basal levels) was prevented in the presence of AMPK activator 5-amino-4-imidazole carboxamide ribonucleotide (AICAR). In keeping, inhibition of AMPK using dorsomorphin or siRNA to AMPKγ increased osteoclast size in control cultures to the level observed in the presence of pyruvate. Thus, we have found that a moderate excess of pyruvate enhances osteoclastogenesis, and that AMPK acts to tailor osteoclastogenesis to a cell's bioenergetics capacity.
Orthogonal Polymer Recognition Based on Semiartificial Helical Polysaccharide
Authors: Numata Munenori , Kinoshita Daiki , Hirose Naoya , Kozawa Tomohiro , Tamiaki Hitoshi 
Published: February 2013

Abstract
Two kinds of polymeric nanoarchitectures, i.e., one-dimensional polymer composites and two-dimensional sheet-like structures, can be created using a semiartificial helical polysaccharide with one-dimensional cavities and peripheral molecular-recognition sites.
Selective Desorption by 4,6-Dimethyldibenzothiophene Addition during Carbazole Hydrodenitrogenation on Sulfided Phosphorus-doped NiMo/Al2O3 Catalyst
Authors: Nagai Masatoshi , Tominaga Hiroyuki , Sugai Daiki 
Published: February 2013

Abstract
The addition of 4,6-dimethyldibenzothiophene at 10 times the molar ratio to carbazole during carbazole hydrodenitrogenation caused bicyclohexyl, 2-ethylbicyclo[4.4.0]decane and hexylcyclohexane to desorb at the amount of 7.88 µmol g·cat−1 from one site of the sulfided 3.5 wt % phosphorus-doped NiMo/Al2O3 catalyst, while the other site remained unaffected by the addition. The number of special adsorption sites for the 4,6-dimethyldibenzothiophene was estimated.
All-Cause and Cardiovascular Mortality in Middle-Aged People With Type 2 Diabetes Compared With People Without Diabetes in a Large U.K. Primary Care Database
Authors: Taylor Kathryn S. , Heneghan Carl J. , Farmer Andrew J. , Fuller Alice M. , Adler Amanda I. , Aronson Jeffrey K. , Stevens Richard J. 
Published: February 2013

OBJECTIVE
Middle-aged people with diabetes have been reported to have significantly higher risks of cardiovascular events than people without diabetes. However, recent falls in cardiovascular disease rates and more active management of risk factors may have abolished the increased risk. We aimed to provide an up-to-date assessment of the relative risks associated with type 2 diabetes of all-cause and cardiovascular mortality in middle-aged people in the U.K.

RESEARCH DESIGN AND METHODS
Using data from the General Practice Research Database, from 2004 to 2010, we conducted a cohort study of 87,098 people, 40–65 years of age at baseline, comparing 21,798 with type 2 diabetes and 65,300 without diabetes, matched on age, sex, and general practice. We produced hazard ratios (HRs) for mortality and compared rates of blood pressure testing, cholesterol monitoring, and use of aspirin, statins, and antihypertensive drugs.

RESULTS
People with type 2 diabetes, compared with people without diabetes, had a twofold increased risk of all-cause mortality (HR 2.07 [95% CI 1.95–2.20], adjusted for smoking) and a threefold increased risk of cardiovascular mortality (3.25 [2.87–3.68], adjusted for smoking). Women had a higher relative risk than men, and people &lt;55 years of age had a higher relative risk than those &gt;55 years of age. Monitoring and medication rates were higher in those with diabetes (all P &lt; 0.001).

CONCLUSIONS
Despite efforts to manage risk factors, administer effective treatments, and develop new therapies, middle-aged people with type 2 diabetes remain at significantly increased risk of death.
Phosphine‐Free Palladium‐Catalyzed Decarboxylative Coupling of Alkynylcarboxylic Acids with Aryl and Heteroaryl Halides
Authors: Reddy Police Vishnuvardhan , Srinivas Pottabathula , Annapurna Manne , Bhargava Suresh , Wagler Jorg , Mirzadeh Nedaossadat , Kantam Mannepalli Lakshmi 
Published: February 2013

AbstractWe herein report the design and development of a carboxyamido/carbene ligand and its Pd‐complex for the decarboxylative coupling of alkynylcarboxylic acids with aryl and heteroaryl halides to afford arylalkynes.
Use of a Semihollow‐Shaped Triethynylphosphane Ligand for Efficient Formation of Six‐ and Seven‐Membered Ring Ethers through Gold(I)‐Catalyzed Cyclization of Hydroxy‐Tethered Propargylic Esters
Authors: Ito Hideto , Harada Ayumi , Ohmiya Hirohisa , Sawamura Masaya 
Published: February 2013

AbstractThe formation of six‐ and seven‐membered ring ethers from hydroxy‐tethered propargylic esters was efficiently catalyzed by a cationic gold(I) complex with a semihollow‐shaped triethynylphosphane ligand. This gold catalysis showed a tolerance toward the reactions of primary, secondary, and tertiary alcohol substrates with various substitution patterns. A sterically congested 2,2,6,6‐tetraalkyl‐substituted tetrahydropyran derivative as well as 6,6‐ and 7,6‐fused bicyclic diethers were obtained in useful yields. In addition, the gold catalysis was applicable to the reaction of a sulfonamide‐tethered propargylic ester to give a piperidine derivative.
Using Conveniently Designed α‐Amino Ketones in Michael Reactions under Iminium Catalysis: Enantioselective Synthesis of γ‐Lactams and γ‐Amino‐δ‐keto Esters
Authors: Talavera Garazi , Reyes Efraím , Vicario Jose L. , Carrillo Luisa , Uria Uxue 
Published: February 2013

AbstractThe behaviour of aminoacetophenones as Michael donors in catalytic enantioselective Michael reactions with α,β‐unsaturated aldehydes under iminium activation has been studied. These compounds react with each other in the presence of catalytic amounts of a chiral secondary amine through a Michael/hemiaminal formation cascade process which proceeds with high yields and enantiocontrol. Elaboration of these adducts by oxidation allows the easy access to chiral disubstituted γ‐lactams and other synthetically useful chiral building blocks such as γ‐amino‐δ‐keto esters or β‐substituted δ‐oxoamides are accessible from the obtained adducts by simple transformations.
Room Temperature Palladium‐Catalyzed Decarboxylative Acyl/Aroylation using [Fe(III)(EDTA)(η2‐O2)]3− as Oxidant at Biological pH
Authors: Sharma Sugandha , Khan Imran A. , Saxena Anil K. 
Published: February 2013

AbstractThe purple‐coloured iron peroxo complex [Fe(III)EDTA(η2‐O2)]3− as a novel reagent system for Pd‐catalyzed decarboxylative ortho‐acylation of acetanilides with α‐oxocarboxylic acids at room temperature in aqueous media has been realized. This reaction provides an effective access to ortho‐acylacetanilides under mild conditions.
Asymmetric Price Transmission in Food Supply Chains: Impulse Response Analysis by Local Projections Applied to U.S. Broiler and Pork Prices
Authors: Kuiper W. Erno , Lansink Alfons G.J.M. Oude 
Published: February 2013

ABSTRACTIn this article, the author's set out Jordà's (2005) method of local projections by which nonlinear/ asymmetric impulse responses can be computed without the need to specify and estimate the underlying nonlinear/asymmetric dynamic system. The method is used to compute price‐reaction functions that show how the prices of the different stages in a food supply chain dynamically respond to each other and whether or not these responses reveal any asymmetric patterns. Empirical applications for the U.S. pork‐meat and broiler‐composite chains illustrate the convenience of the method and reveal that in the pork chain asymmetric price transmission enables retailers (wholesalers) to increase their marketing margin vis‐à‐vis the wholesalers (farmers), whereas in the broiler sector the retailers face both temporary decreases and increases in their marketing margin as a consequence of asymmetric wholesale‐retail price transmission.