bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight loss with liraglutide, a once‐daily human glucagon‐like peptide‐1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue
Authors: Jendle J. , Nauck M. A. , Matthews D. R. , Frid A. , Hermansen K. , Düring M. , Zdravkovic M. , Strauss B. J. , Garber A. J. ,   on behalf of the LEAD‐2 and LEAD‐3 Study Groups
Published: September 2009

Aim: The effect on body composition of liraglutide, a once‐daily human glucagon‐like peptide‐1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D). Methods: These were randomized, double‐blind, parallel‐group trials of 26 [Liraglutide Effect and Action in Diabetes‐2 (LEAD‐2)] and 52 weeks (LEAD‐3). Patients with T2D, aged 18–80 years, body mass index (BMI) ≤40 kg/m2 (LEAD‐2), ≤45 kg/m2 (LEAD‐3) and HbA1c 7.0–11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5–2 g/day in LEAD‐2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD‐3. LEAD‐2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD‐2: adipose tissue area and hepatic steatosis were assessed. Results: LEAD‐2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver‐to‐spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD‐3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01). Conclusion: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.
Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT‐551
Authors: Fukuda S. , Ohta T. , Sakata S. , Morinaga H. , Ito M. , Nakagawa Y. , Tanaka M. , Matsushita M. 
Published: September 2009

Aim: Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling, is a novel therapeutic target for type 2 diabetes mellitus. We evaluated in vitro and in vivo the pharmacological profiles of a new PTP1B inhibitor, JTT‐551: monosodium ({[5‐(1,1‐dimethylethyl)thiazol‐2‐yl]methyl} {[(4‐{4‐[4‐(1‐propylbutyl)phenoxy]methyl}phenyl)thiazol‐2‐yl]methyl}amino)acetate. Methods: PTP1B inhibitory activity and the inhibition mode were assayed with p‐nitrophenyl phosphate as a substrate, and the selectivity of JTT‐551 against other PTPs, including T‐cell protein tyrosine phosphatase (TCPTP), CD45 protein tyrosine phosphatase (CD45) and leucocyte common antigen‐related protein tyrosine phosphatase (LAR), was evaluated. Glucose uptake with JTT‐551 treatment was evaluated in L6 rat skeletal myoblasts (L6 cells). In the in vivo study, we investigated the effects on insulin receptor (IR) phosphorylation and blood chemical parameters with JTT‐551 administration in ob/ob mice and db/db mice. Results: JTT‐551 showed an inhibitory effect on PTP1B with a Ki value of 0.22 µM, and a mixed‐type inhibition mode. Ki values of TCPTP, CD45 and LAR were 9.3, 30 or higher and 30 or higher µM, respectively, and JTT‐551 exhibited clear selectivity against the other PTPs. Moreover, JTT‐551 increased the insulin‐stimulated glucose uptake in L6 cells. A single administration of JTT‐551 in ob/ob mice enhanced the IR phosphorylation of liver and reduced the glucose level. In db/db mice, chronic administration showed a hypoglycaemic effect without an acceleration of body weight gain. Conclusions: JTT‐551, a newly developed PTP1B inhibitor, improves glucose metabolism by enhancement of insulin signalling and could be useful in the treatment of type 2 diabetes mellitus.
Mortality of Life‐Insured Swedish Cats during 1999–2006: Age, Breed, Sex, and Diagnosis
Authors: Egenvall A. , Nødtvedt A. , Häggström J. , Ström Holst B. , Möller L. , Bonnett B.N. 
Published: September 2009

Background: A cat life insurance database can potentially be used to study feline mortality.Hypothesis: The aim was to describe patterns of mortality in life‐insured Swedish cats.Cats: All cats (<13 years of age) with life insurance during the period 1999–2006 were included.Methods: Age‐standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed.Results: The total number of cats insured was 49,450 and the number of cat‐years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431–493). Sex‐specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed‐specific (for most breeds) survival increased with time when analyzed by 2‐year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed.Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.
Role of AbeS, a Novel Efflux Pump of the SMR Family of Transporters, in Resistance to Antimicrobial Agents in
Acinetobacter baumannii
Authors: Srinivasan Vijaya Bharathi , Rajamohan Govindan , Gebreyes Wondwossen A. 
Published: September 2009

ABSTRACT

In this study, a chromosomally encoded putative drug efflux pump of the SMR family, named AbeS, from a multidrug-resistant strain of
Acinetobacter baumannii
was characterized to elucidate its role in antimicrobial resistance. Expression of the cloned
abeS
gene in hypersensitive
Escherichia coli
host KAM32 resulted in decreased susceptibility to various classes of antimicrobial agents, detergents, and dyes. Deletion of the
abeS
gene in
A. baumannii
confirmed its role in conferring resistance to these compounds.
Detection of the Novel Extended-Spectrum β-Lactamase OXA-161 from a Plasmid-Located Integron inPseudomonas aeruginosaClinical Isolates from Spain
Authors: Juan C. , Mulet X. , Zamorano L. , Albertí S. , Pérez J. L. , Oliver A. 
Published: September 2009

ABSTRACTTwo clonally relatedPseudomonasaeruginosaisolates, recovered from two patients admitted to a pediatric intensive care unit, were found to harbor a new OXA-2 variant (Asn148Asp), designated OXA-161. The plasmid location ofblaOXA-161was demonstrated through electroporation to PAO1, and its codification in a class I integron (together withaacA4) was demonstrated through PCR and sequencing.blaOXA-2andblaOXA-161were cloned in parallel to demonstrate the extended-spectrum β-lactamase properties of OXA-161, conferring resistance to ceftazidime and reduced susceptibility to cefepime and aztreonam.
The Final Step of Hygromycin A Biosynthesis, Oxidation of C-5″-Dihydrohygromycin A, Is Linked to a Putative Proton Gradient-Dependent Efflux
Authors: Dhote Vidya , Starosta Agata L. , Wilson Daniel N. , Reynolds Kevin A. 
Published: September 2009

ABSTRACTHygromycin A (HA) is an aminocyclitol antibiotic produced and excreted byStreptomyces hygroscopicus. Deletion ofhyg26from the hygromycin A biosynthetic gene cluster has previously been shown to result in a mutant that produces 5″-dihydrohygromycin A (DHHA). We report herein on the purification and characterization of Hyg26 expressed inEscherichiacoli. The enzyme catalyzes an NAD(H)-dependent reversible interconversion of HA and DHHA, supporting the role of the reduced HA as the penultimate biosynthetic pathway intermediate and not a shunt product. The equilibrium for the Hyg26-catalyzed reaction heavily favors the DHHA intermediate. The high-titer production of the HA product byS. hygroscopicusmust be dependent upon a subsequent energetically favorable enzyme-catalyzed process, such as the selective and efficient export of HA.hyg19encodes a putative proton gradient-dependent transporter, and a mutant lacking this gene was observed to produce less HA and to produce the DHHA intermediate. The DHHA produced by either the Δhyg19or the Δhyg26mutant had slightly reduced activity againstE. coliand reduced protein synthesis-inhibitory activity in vitro. The data indicate that Hyg26 and Hyg19 have evolved to produce and export the final potent HA product in a coordinated fashion.
Pepper Mild Mottle Virus
as an Indicator of Fecal Pollution
Authors: Rosario Karyna , Symonds Erin M. , Sinigalliano Christopher , Stewart Jill , Breitbart Mya 
Published: September 2009

ABSTRACT

Accurate indicators of fecal pollution are needed in order to minimize public health risks associated with wastewater contamination in recreational waters. However, the bacterial indicators currently used for monitoring water quality do not correlate with the presence of pathogens. Here we demonstrate that the plant pathogen
Pepper mild mottle virus
(PMMoV) is widespread and abundant in wastewater from the United States, suggesting the utility of this virus as an indicator of human fecal pollution. Quantitative PCR was used to determine the abundance of PMMoV in raw sewage, treated wastewater, seawater exposed to wastewater, and fecal samples and/or intestinal homogenates from a wide variety of animals. PMMoV was present in all wastewater samples at concentrations greater than 1 million copies per milliliter of raw sewage. Despite the ubiquity of PMMoV in human feces, this virus was not detected in the majority of animal fecal samples tested, with the exception of chicken and seagull samples. PMMoV was detected in four out of six seawater samples collected near point sources of secondary treated wastewater off southeastern Florida, where it co-occurred with several other pathogens and indicators of fecal pollution. Since PMMoV was not found in nonpolluted seawater samples and could be detected in surface seawater for approximately 1 week after its initial introduction, the presence of PMMoV in the marine environment reflects a recent contamination event. Together, these data demonstrate that PMMoV is a promising new indicator of fecal pollution in coastal environments.
Molecular Characterization of Bacteriophages for Microbial Source Tracking in Korea
Authors: Lee Jung Eun , Lim Mi Young , Kim Sei Yoon , Lee Sunghee , Lee Heetae , Oh Hyun-Myung , Hur Hor-Gil , Ko GwangPyo 
Published: September 2009

ABSTRACT

We investigated coliphages from various fecal sources, including humans and animals, for microbial source tracking in South Korea. Both somatic and F
+
-specific coliphages were isolated from 43 fecal samples from farms, wild animal habitats, and human wastewater plants. Somatic coliphages were more prevalent and abundant than F
+
coliphages in all of the tested fecal samples. We further characterized 311 F
+
coliphage isolates using RNase sensitivity assays, PCR and reverse transcription-PCR, and nucleic acid sequencing. Phylogenetic analyses were performed based on the partial nucleic acid sequences of 311 F
+
coliphages from various sources. F
+
RNA coliphages were most prevalent among geese (95%) and were least prevalent in cows (5%). Among the genogroups of F
+
RNA coliphages, most F
+
coliphages isolated from animal fecal sources belonged to either group I or group IV, and most from human wastewater sources were in group II or III. Some of the group I coliphages were present in both human and animal source samples. F
+
RNA coliphages isolated from various sources were divided into two main clusters. All F
+
RNA coliphages isolated from human wastewater were grouped with Qβ-like phages, while phages isolated from most animal sources were grouped with MS2-like phages. UniFrac significance statistical analyses revealed significant differences between human and animal bacteriophages. In the principal coordinate analysis (PCoA), F
+
RNA coliphages isolated from human waste were distinctively separate from those isolated from other animal sources. However, F
+
DNA coliphages were not significantly different or separate in the PCoA. These results demonstrate that proper analysis of F
+
RNA coliphages can effectively distinguish fecal sources.
The Olive Fly Endosymbiont, “CandidatusErwinia dacicola,” Switches from an Intracellular Existence to an Extracellular Existence during Host Insect Development
Authors: Estes Anne M. , Hearn David J. , Bronstein Judith L. , Pierson Elizabeth A. 
Published: September 2009

ABSTRACTAs polyphagous, holometabolous insects, tephritid fruit flies (Diptera: Tephritidae) provide a unique habitat for endosymbiotic bacteria, especially those microbes associated with the digestive system. Here we examine the endosymbiont of the olive fly [Bactrocera oleae(Rossi) (Diptera: Tephritidae)], a tephritid of great economic importance. “CandidatusErwinia dacicola” was found in the digestive systems of all life stages of wild olive flies from the southwestern United States. PCR and microscopy demonstrated that “Ca.Erwinia dacicola” resided intracellularly in the gastric ceca of the larval midgut but extracellularly in the lumen of the foregut and ovipositor diverticulum of adult flies. “Ca.Erwinia dacicola” is one of the few nonpathogenic endosymbionts that transitions between intracellular and extracellular lifestyles during specific stages of the host's life cycle. Another unique feature of the olive fly endosymbiont is that unlike obligate endosymbionts of monophagous insects, “Ca.Erwinia dacicola” has a G+C nucleotide composition similar to those of closely related plant-pathogenic and free-living bacteria. These two characteristics of “Ca.Erwinia dacicola,” the ability to transition between intracellular and extracellular lifestyles and a G+C nucleotide composition similar to those of free-living relatives, may facilitate survival in a changing environment during the development of a polyphagous, holometabolous host. We propose that insect-bacterial symbioses should be classified based on the environment that the host provides to the endosymbiont (the endosymbiont environment).
Hydroxylation and Further Oxidation of Δ9-Tetrahydrocannabinol by Alkane-Degrading Bacteria
Authors: Rashidi Hassan , Akhtar Muhammad T. , van der Kooy Frank , Verpoorte Robert , Duetz Wouter A. 
Published: September 2009

ABSTRACTThe microbial biotransformation of Δ9-tetrahydrocannabinol was investigated using a collection of 206 alkane-degrading strains. Fifteen percent of these strains, mainly gram-positive strains from the generaRhodococcus,Mycobacterium,Gordonia, andDietzia, yielded more-polar derivatives. Eight derivatives were produced on a mg scale, isolated, and purified, and their chemical structures were elucidated with the use of liquid chromatography-mass spectrometry,1H-nuclear magnetic resonance (1H-NMR), and two-dimensional NMR (1H-1H correlation spectroscopy and heteronuclear multiple bond coherence). All eight biotransformation products possessed modified alkyl chains, with hydroxy, carboxy, and ester functionalities. In a number of strains, β-oxidation of the initially formed C5carboxylic acid led to the formation of a carboxylic acid lacking two methylene groups.
Bacterial Community Composition of Stream Biofilms in Spatially Variable-Flow Environments
Authors: Besemer Katharina , Singer Gabriel , Hödl Iris , Battin Tom J. 
Published: September 2009

ABSTRACT
Streams are highly heterogeneous ecosystems, in terms of both geomorphology and hydrodynamics. While flow is recognized to shape the physical architecture of benthic biofilms, we do not yet understand what drives community assembly and biodiversity of benthic biofilms in the heterogeneous flow landscapes of streams. Within a metacommunity ecology framework, we experimented with streambed landscapes constructed from bedforms in large-scale flumes to illuminate the role of spatial flow heterogeneity in biofilm community composition and biodiversity in streams. Our results show that the spatial variation of hydrodynamics explained a remarkable percentage (up to 47%) of the variation in community composition along bedforms. This suggests species sorting as a model of metacommunity dynamics in stream biofilms, though natural biofilm communities will clearly not conform to a single model offered by metacommunity ecology. The spatial variation induced by the hydrodynamics along the bedforms resulted in a gradient of bacterial beta diversity, measured by a range of diversity and similarity indices, that increased with bedform height and hence with spatial flow heterogeneity at the flume level. Our results underscore the necessity to maintain small-scale physical heterogeneity for community composition and biodiversity of biofilms in stream ecosystems.
Low Taxon Richness of Bacterioplankton in High-Altitude Lakes of the Eastern Tibetan Plateau, with a Predominance ofBacteroidetesandSynechococcusspp
Authors: Xing Peng , Hahn Martin W. , Wu Qinglong L. 
Published: September 2009

ABSTRACTPlankton samples were collected from six remote freshwater and saline lakes located at altitudes of 3,204 to 4,718 m and 1,000 km apart within an area of ca. 1 million km2on the eastern Tibetan Plateau to comparatively assess how environmental factors influence the diversity of bacterial communities in high-altitude lakes. The composition of the bacterioplankton was investigated by analysis of large clone libraries of 16S rRNA genes. Comparison of bacterioplankton diversities estimated for the six Tibetan lakes with reference data previously published for lakes located at lower altitudes indicated relatively low taxon richness in the Tibetan lakes. The estimated average taxon richness in the four Tibetan freshwater lakes was only one-fifth of the average taxon richness estimated for seven low-altitude reference lakes. This cannot be explained by low coverage of communities in the Tibetan lakes by the established libraries or by differences in habitat size. Furthermore, a comparison of the taxonomic compositions of bacterioplankton across the six Tibetan lakes revealed low overlap between their community compositions. About 70.9% of the operational taxonomic units (99% similarity) were specific to single lakes, and a relatively high percentage (11%) of sequences were <95% similar to publicly deposited sequences of cultured or uncultured bacteria. This beta diversity was explained by differences in salinity between lakes rather than by distance effects. Another characteristic of the investigated lakes was the predominance ofCyanobacteria(Synechococcus) andBacteroidetes. These features of bacterioplankton diversity may reflect specific adaptation of various lineages to the environmental conditions in these high-altitude lakes.
UropathogenicEscherichia coliSuppresses the Host Inflammatory Response via Pathogenicity Island GenessisAandsisB
Authors: Lloyd Amanda L. , Smith Sara N. , Eaton Kathryn A. , Mobley Harry L. T. 
Published: September 2009

ABSTRACTExtraintestinal pathogenicEscherichia colican successfully colonize the urinary tract of the immunocompetent host. In part, this is accomplished by dampening the host immune response. Indeed, thesisAandsisBgenes (shiA-likeinflammationsuppressor genesAandB) of uropathogenicE. colistrain CFT073, homologs of theShigella flexneriSHI-2 pathogenicity island geneshiA, suppress the host inflammatory response. A double deletion mutant (ΔsisAΔsisB) resulted in a hyperinflammatory phenotype in an experimental model of ascending urinary tract infection. The ΔsisAΔsisBmutant not only caused significantly more inflammatory foci in the kidneys of CBA/J mice (P= 0.0399), but these lesions were also histologically more severe (P= 0.0477) than lesions observed in mice infected with wild-type CFT073. This hyperinflammatory phenotype could be suppressed to wild-type levels by in vivo complementation of the ΔsisAΔsisBmutant with either thesisAorsisBgene intrans. The ΔsisAΔsisBmutant was outcompeted by wild-type CFT073 during cochallenge infection in the bladder (P= 0.0295) at 48 h postinoculation (hpi). However, during cochallenge infections, we reasoned that wild-type CFT073 could partially complement the ΔsisAΔsisBmutant. Consistent with this, the most significant colonization defect of the ΔsisAΔsisBmutant in vivo was observed during independent challenge relative to wild-type CFT073, with attenuation of the mutant observed in the bladder (P< 0.0001) and kidneys (P= 0.0003) at 6 hpi. By 24 and 48 hpi, the ΔsisAΔsisBmutant was no longer significantly attenuated in the bladder or kidneys, suggesting that thesisAandsisBgenes may be important for suppressing the host immune response during the initial stages of infection.
Complement Receptor 3 Deficiency Influences Lesion Progression duringLeishmania majorInfection in BALB/c Mice
Authors: Carter Cristina R. , Whitcomb James P. , Campbell Jessica A. , Mukbel Rami M. , McDowell Mary Ann 
Published: September 2009

ABSTRACTLeishmania majoris an obligately intracellular protozoan parasite that causes cutaneous leishmaniasis. Like numerous intracellular pathogens,Leishmaniaexploits cell surface receptors as a means of entry into host cells. Complement receptor 3 (CR3; also called CD11b/CD18), a β2integrin on phagocytic cells, is one such receptor. Ligation of CR3 has been shown to inhibit the production of interleukin-12, the cytokine that is pivotal in establishing the cell-mediated response necessary to combat intracellular infection. Here we investigate the role that CR3 plays in the establishment and progression of cutaneous leishmaniaisis in vivo. Dermal lesions of wild-type BALB/c mice are characteristically progressive and lead to extensive tissue necrosis coupled with elevated parasite burdens; CD11b-deficient BALB/c mice, however, demonstrate an intermediate phenotype characterized by chronic lesions and a reduced incidence of tissue damage. Infection followed by a reinfection challenge indicates that both susceptible (BALB/c) and resistant (C57BL/6) mice, regardless of CD11b status, develop resistance toL. major. In addition, CD11b does not bias the T helper cytokine response toL. majorinfection. Our results further indicate that CD11b is not necessary for disease resolution in resistant mice; rather, this protein appears to play a minor role in susceptibility.
σXIs Involved in ControllingBacillus subtilisBiofilm Architecture through the AbrB Homologue Abh
Authors: Murray Ewan J. , Strauch Mark A. , Stanley-Wall Nicola R. 
Published: September 2009

ABSTRACTA characteristic feature of biofilm formation is the production of a protective extracellular polymeric matrix. In the gram-positive bacteriumBacillus subtilis, the biofilm matrix is synthesized by the products of theepsABCDEFGHIJKLMNOoperon (hereafter called theepsoperon) andyqxM-sipW-tasAloci. Transcription from these operons is repressed by two key regulators, AbrB and SinR. Relief of inhibition is necessary to allow biofilm formation to proceed. Here we present data indicating that Abh, a sequence and structural homologue of AbrB, regulates biofilm architecture byB.subtiliswhen colony morphology and pellicle formation are assessed. Data indicating thatabhexpression is dependent on the environmental signals that stimulate the activity of the extracytoplasmic function σ-factor σXare shown. We demonstrate that expression ofslrR, the proposed activator ofyqxMtranscription, is positively controlled by Abh. Furthermore, Abh is shown to activate transcription from the promoter of theepsoperon through its control of SlrR. These findings add to the increasingly complex transcriptional network that controls biofilm formation byB.subtilis.